Study Unit 1

Here's a breakdown of the key points:

Types of Chemical Messengers:

1. Neurotransmitters: Released by nerve cells, acting locally to influence other

nerve cells.
2. Endocrine Hormones: Secreted by glands into the bloodstream, affecting
target cells at distant locations.
3. Neuroendocrine Hormones: Produced by neurons and released into the
bloodstream, influencing distant target cells.
4. Paracrines: Secreted by cells, affecting nearby cells of a different type.
5. Autocrines: Secreted by cells, affecting themselves.
6. Cytokines: Can act as autocrines, paracrines, or even endocrine hormones,
playing a role in the immune system. Examples include interleukins and leptin.

Focus on Endocrine and Neuroendocrine Systems:

The passage highlights these two systems for detailed discussion later, noting their
interaction for maintaining homeostasis (stable internal environment).

Examples of Hormone Action:

• Growth hormone (anterior pituitary) promotes growth throughout the body.

• Thyroxine (thyroid gland) increases the rate of cellular reactions.
• Insulin (pancreas) allows cells to use glucose for energy.
• Sex hormones (ovaries/testes) control sexual development and function.

Chemical Structure and Synthesis of Hormones:

• Three main classes:

o Proteins/Polypeptides (e.g., insulin, growth hormone)
o Steroids (e.g., cortisol, testosterone)
o Derivatives of tyrosine (e.g., thyroxine, epinephrine)
• Protein/Polypeptide Hormones:
o Synthesized and stored in vesicles.
o Released by exocytosis upon stimulation (e.g., increased calcium or
receptor activation).
o Water-soluble for easy transport in blood.
• Steroid Hormones:
o Derived from cholesterol.
o Lipid-soluble and not stored.

Overall Importance:

Hormones play a critical role in regulating nearly all bodily functions, including
metabolism, growth, development, fluid balance, reproduction, and behavior.
The body's various activities are coordinated through different chemical messenger
systems. These include:

1. **Neurotransmitters:** Released by neurons into synaptic junctions to control

nerve cell functions locally.

2. **Endocrine hormones:** Released by glands or specialized cells into the

bloodstream to influence target cells at another location in the body.

3. **Neuroendocrine hormones:** Secreted by neurons into the bloodstream to

influence target cells at another location.

4. **Paracrines:** Secreted by cells into the extracellular fluid to affect neighboring

target cells of a different type.

5. **Autocrines:** Secreted by cells into the extracellular fluid to affect the function of
the same cells that produced them.
6. **Cytokines:** Peptides secreted by cells into the extracellular fluid, which can
function as autocrines, paracrines, or endocrine hormones. Examples include
interleukins and other lymphokines secreted by helper cells, which act on other cells
of the immune system. Adipocytes also produce cytokine hormones, sometimes
called adipokines, such as leptin.

These messenger systems interact to maintain homeostasis. For instance, the

adrenal medullae and the pituitary gland secrete hormones primarily in response to
neural stimuli. Neuroendocrine cells in the hypothalamus secrete neurohormones
that control the secretion of anterior pituitary hormones. Endocrine hormones are
carried by the circulatory system to cells throughout the body, where they bind with
receptors and initiate cell reactions.

Hormones can broadly affect the body's functions, including metabolism, growth and
development, water and electrolyte balance, reproduction, and behavior. For
example, growth hormone from the anterior pituitary gland stimulates growth in most
body parts, while thyroxine from the thyroid gland increases the rate of many
chemical reactions in almost all body cells.

There are three general classes of hormones:

1. **Proteins and polypeptides:** Include hormones from the anterior and posterior
pituitary gland, pancreas (insulin and glucagon), and parathyroid gland (parathyroid
hormone).
2. **Steroids:** Secreted by the adrenal cortex, ovaries, testes, and placenta.

3. **Amine hormones:** Derived from the amino acid tyrosine, including thyroid and
adrenal medullary hormones.

Protein and peptide hormones are stored in secretory vesicles until needed, while
steroid hormones are synthesized from cholesterol and not stored. Amine hormones
are derived from tyrosine. Hormones are crucial for regulating body functions, and
their absence can lead to significant health issues.

Synthesis and Storage of Different Hormone Types:

The passage describes how different types of hormones are synthesized and stored
in the body:

Steroid Hormones:

• Made from cholesterol and stored in very low quantities.

• Large cholesterol reserves are present in vacuoles for rapid mobilization upon
stimulation.
• Some cholesterol comes from blood plasma, while some is synthesized within
the cell.
• Highly lipid-soluble, allowing them to diffuse freely across cell membranes
after synthesis and enter the bloodstream.

Amine Hormones derived from Tyrosine:

• Two main groups: thyroid hormones and adrenal medullary hormones.

• Produced by enzymes in the cytoplasm of glandular cells.

Thyroid Hormones:

• Synthesized, stored within the thyroid gland, and incorporated into a protein
called thyroglobulin.
• Thyroglobulin is stored in large follicles.
• Hormone secretion occurs when amines are cleaved from thyroglobulin,
releasing them into the bloodstream.
• Most thyroid hormones then bind to plasma proteins for slow release to target
tissues.

Adrenal Medullary Hormones (Epinephrine and Norepinephrine):

• Formed in the adrenal medulla.

• Stored in preformed vesicles before secretion.
• Released by exocytosis upon stimulation.
 • Can circulate freely in the blood or be bound to other substances.

The body's hormone systems are diverse and play crucial roles in regulating various
physiological functions. Here's a detailed summary of the information provided:

**Adrenal Cortex:**

- **Cortisol:** Controls metabolism of proteins, carbohydrates, and fats, and has anti-
inflammatory effects.

- **Aldosterone:** Increases renal sodium reabsorption, potassium secretion, and

hydrogen ion secretion.

**Adrenal Medulla:**
- **Norepinephrine, epinephrine:** Have the same effects as sympathetic stimulation.

**Pancreas:**

- **Insulin (beta cells):** Promotes glucose entry into cells, controlling carbohydrate
metabolism.

- **Glucagon (α cells):** Increases synthesis and release of glucose from the liver
into body fluids.

**Parathyroid:**

- **Parathyroid hormone:** Controls serum calcium ion concentration by increasing

calcium absorption by the gut and kidneys, and releasing calcium from bones.

**Testes:**

- **Testosterone:** Promotes development of the male reproductive system and male

secondary sexual characteristics.

**Ovaries:**

- **Estrogens:** Promote growth and development of the female reproductive

system, female breasts, and female secondary sexual characteristics.
- **Progesterone:** Stimulates secretion of "uterine milk" by uterine endometrial
glands and promotes development of secretory apparatus of breasts.

**Placenta:**

- **Human chorionic gonadotropin:** Promotes growth of corpus luteum and

secretion of estrogens and progesterone by corpus luteum.

- **Human somatomammotropin:** Probably helps promote development of some

fetal tissues, as well as the mother’s breasts.

**Kidney:**

- **Renin:** Catalyzes conversion of angiotensinogen to angiotensin I (acts as an

enzyme).

- **1,25-Dihydroxycholecalciferol:** Increases intestinal absorption of calcium and

bone mineralization.

- **Erythropoietin:** Increases erythrocyte production.

**Heart:**

- **Atrial natriuretic peptide:** Increases sodium excretion by kidneys, reduces blood

pressure.

**Stomach:**

- **Gastrin:** Stimulates hydrogen chloride secretion by parietal cells.

**Small Intestine:**

- **Secretin:** Stimulates pancreatic acinar cells to release bicarbonate and water.

- **Cholecystokinin:** Stimulates gallbladder contraction and release of pancreatic

enzymes.

**Adipocytes:**
- **Leptin:** Inhibits appetite, stimulates thermogenesis.
**Hormone Secretion and Feedback:**

- Hormones have different onset and duration of action, ranging from seconds to
months.

- Negative feedback mechanisms control hormone activity to prevent overactivity.

- Positive feedback can cause surges in hormone secretion.

- Cyclical variations in hormone release occur due to various factors like seasonal
changes, development stages, diurnal cycle, and sleep patterns.

**Transport of Hormones:**
- Water-soluble hormones are dissolved in plasma and transported directly to target
tissues.

- Steroid and thyroid hormones circulate bound to plasma proteins and are
biologically inactive until they dissociate.

- Hormones bound to plasma proteins serve as reservoirs, affecting hormone

clearance and availability.

Hormones play critical roles in regulating various physiological functions, and their
secretion, transport, and feedback mechanisms are tightly controlled to maintain
homeostasis in the body.

Hormone Secretion, Transport, and Clearance

This passage discusses how hormones are secreted, transported in the

bloodstream, and eventually cleared from the body.

Secretion and Duration of Action:

• Hormones have varying response times:

o Some, like epinephrine, act within seconds.
o Others, like thyroxine, take months for full effect.

Concentration in Blood:

• Hormone concentrations are incredibly small (picograms to micrograms per

milliliter).
• Specialized mechanisms allow these minute quantities to have a significant
effect.

Feedback Control:

• Negative feedback is the primary control mechanism:

 o Hormone action suppresses further release of that hormone.
o This feedback can occur at various stages of hormone production and
release.
• Positive feedback loops exist in some cases (e.g., LH surge before ovulation).

Cyclical Variations:

• Hormone release can be influenced by:

o Seasons
o Development stages
o Daily cycles (diurnal rhythm)
o Sleep patterns
• The suprachiasmatic nucleus (SCN) acts as a "master clock" for these cycles.
• Local clocks in some endocrine tissues also contribute.
• Cyclical changes allow the body to adapt to daily variations in stress and
demands.
• In females, cyclical changes in sex hormones are essential for reproduction.

Transport in Blood:

• Water-soluble hormones travel freely in the plasma.

• Steroid and thyroid hormones bind to plasma proteins for transport.
• Bound hormones are inactive but act as a reservoir, replenishing free
hormone levels.
• Binding slows clearance from the bloodstream.

Clearance from Blood:

• Clearance depends on:

o Rate of hormone secretion
o Rate of hormone removal from the blood (which is not discussed in the
provided excerpt).
o Clearance mechanisms likely involve hormone metabolism and
excretion.

Overall, this passage highlights the complex interplay between hormone

secretion, transport, and clearance to maintain precise hormonal control
within the body.

Metabolic clearance rate (MCR) is a measure of how quickly a hormone is removed

from the blood. It is typically expressed in terms of the volume of plasma cleared of
the hormone per minute. To calculate MCR, one needs to know the rate at which the
hormone disappears from the plasma and the plasma concentration of the hormone.
The formula for MCR is:

\[MCR = \frac{Rate \ of \ disappearance \ of \ hormone \ from \

plasma}{Concentration \ of \ hormone}\]
To measure MCR, a purified solution of the hormone tagged with a radioactive
substance is infused into the bloodstream at a constant rate until the radioactive
concentration in the plasma becomes steady. The rate of disappearance of the
radioactive hormone from the plasma equals the infusion rate, giving the rate of
disappearance. Simultaneously, the plasma concentration of the radioactive
hormone is measured. Using the formula, MCR can then be calculated.

Hormones are cleared from the plasma through various processes, including
metabolic destruction by tissues, binding with tissues, excretion by the liver into bile,
and excretion by the kidneys into urine. A decreased MCR can lead to an
excessively high concentration of the hormone in body fluids. For example, in liver
disease, decreased MCR can cause accumulation of steroid hormones because
these hormones are mainly cleared into bile after conjugation in the liver.

Peptide hormones and catecholamines, which are water-soluble, circulate freely in

the blood, are degraded by enzymes, and are rapidly excreted by the kidneys and
liver. They remain in the blood for only a short time. Steroid and thyroid hormones,
which are bound to plasma proteins, are cleared from the blood at slower rates and
may remain in circulation for several hours or days. The half-life of adrenal steroids
ranges from 20 to 100 minutes, while protein-bound thyroid hormones can have a
half-life of 1 to 6 days.

Hormone Clearance and Mechanisms of Action

This passage dives into how hormones are removed from the bloodstream and how
they exert their effects on target cells.

Clearance Mechanisms:

• Metabolic clearance rate: This reflects how quickly a hormone is removed

from the blood, measured in ml of plasma cleared per minute.
• Calculation involves disappearance rate and plasma concentration of the
hormone.
• Radioactive tracers are used to measure disappearance rate.
• Clearance mechanisms include:
o Metabolic destruction by tissues
o Binding to tissues
o Liver excretion into bile
o Kidney excretion into urine
• Decreased clearance can lead to abnormally high hormone levels (e.g., liver
disease and steroid hormones).
• Some hormones are degraded at target cells through endocytosis.
• Water-soluble hormones (peptides and catecholamines):
 o Short circulation time due to rapid degradation and excretion.
o Example: Half-life of angiotensin II is less than a minute.
• Protein-bound hormones:
o Slower clearance due to binding with plasma proteins.
o Longer circulation time (hours or days).
o Example: Half-life of adrenal steroids is 20-100 minutes.
o Half-life of protein-bound thyroid hormones is 1-6 days.

Mechanisms of Action:

• Hormone Receptors and Activation:

o The first step is binding to specific receptors on target cells.
o Lack of receptors means no response to the hormone.
o Receptor locations:
▪ Cell membrane (mostly for protein, peptide, and catecholamine
hormones)
▪ Cytoplasm (mainly for steroid hormones)
▪ Nucleus (for thyroid hormones)
o One hormone typically has a specific receptor and vice versa.
o Target tissues have receptors for the hormones that affect them.
• Number and Sensitivity of Hormone Receptors:
o Receptor numbers can change over time.
o Receptor proteins can be inactivated/destroyed or reactivated/newly
made.
o Increased hormone concentration and binding can decrease receptor
number (down-regulation).
▪ This reduces target tissue responsiveness.
o Some hormones can cause up-regulation (increased receptor
formation), making the target tissue more sensitive.
• Intracellular Signaling after Receptor Activation:
o Hormone-receptor complex formation initiates hormonal effects.
o Different types of interactions exist:
▪ Ion Channel-Linked Receptors:
▪ Neurotransmitters like acetylcholine and norepinephrine
bind to these.
▪ Binding opens or closes channels for specific ions (e.g.,
sodium, potassium, calcium).
▪ Altered ion movement affects postsynaptic cells.
▪ Most hormones have indirect effects on ion channels.

This passage emphasizes the intricate interplay between hormone clearance,

receptor interaction, and subsequent cellular responses.

Enzyme-linked receptors are a type of cell surface receptor that activates enzymes
inside the cell upon hormone binding. These receptors have a hormone-binding site
on the outer side of the cell membrane and an enzyme-binding site on the inner side.
Upon hormone binding, the receptor undergoes a conformational change that
activates an enzyme located nearby, initiating a cascade of intracellular signaling
events. This mechanism allows for the amplification of the hormonal signal and the
regulation of various cellular functions.

One example of an enzyme-linked receptor is the leptin receptor, which is activated

by the hormone leptin secreted by fat cells. The leptin receptor belongs to a family of
cytokine receptors that signal through associated enzymes. When leptin binds to its
receptor, it causes a conformational change that activates the enzyme janus kinase
2 (JAK2), which is associated with the receptor. Activated JAK2 then phosphorylates
other proteins, including signal transducer and activator of transcription (STAT)
proteins, leading to the activation of genes involved in appetite regulation and energy
balance.

Another example is the activation of adenylyl cyclase by certain hormones, leading

to the production of cyclic adenosine monophosphate (cAMP), a second messenger
that mediates various cellular responses. Hormones bind to specific receptors
coupled to stimulatory G proteins (Gs proteins), which activate adenylyl cyclase.
Adenylyl cyclase then catalyzes the conversion of ATP to cAMP, which activates
protein kinase A (PKA). PKA phosphorylates target proteins, leading to changes in
cellular function.

Intracellular hormone receptors are another type of receptor that binds to hormones
inside the cell, typically in the cytoplasm or nucleus. These receptors are activated
by lipid-soluble hormones such as steroid hormones, thyroid hormones, and
retinoids. Upon hormone binding, the receptor-hormone complex enters the nucleus
and binds to specific DNA sequences called hormone response elements, regulating
the transcription of target genes and ultimately influencing protein synthesis and
cellular function.

Overall, enzyme-linked receptors play a crucial role in mediating the effects of

hormones on target cells, regulating various physiological processes such as growth,
metabolism, and gene expression. Hormone Signaling Pathways: G Protein-
Coupled vs. Enzyme-Linked Receptors

This passage explains two main mechanisms by which hormones trigger cellular
responses: G protein-coupled receptors and enzyme-linked receptors.

G Protein-Coupled Receptors:

• Most common type of hormone receptor.

• Have seven transmembrane segments.
 • Interact with G proteins (heterotrimeric guanosine triphosphate (GTP)-binding
proteins).
• G proteins have three subunits (α, β, and γ).
• In the inactive state, G proteins bind GDP on the α subunit.

Activation Process:

1. Hormone binds to the receptor's extracellular domain.

2. Receptor conformational change activates the G protein.
3. GDP is exchanged for GTP on the α subunit.
4. Activated α subunit dissociates from β and γ subunits.
5. α subunit interacts with intracellular signaling proteins:
o Opens/closes ion channels
o Changes activity of enzymes (e.g., adenylyl cyclase, phospholipase C)
6. α subunit hydrolyzes GTP to GDP, becoming inactive and reassociating with
β and γ subunits.
7. Hormone dissociation terminates the signaling event.

Types of G Proteins:

• Gi proteins: Inhibitory - decrease activity of target enzymes.

• Gs proteins: Stimulatory - increase activity of target enzymes.

Enzyme-Linked Receptors:

• Less common than G protein-coupled receptors.

• Have only one transmembrane segment.
• Act as enzymes or are closely associated with enzymes.
• Hormone binding site is on the outside of the cell membrane.
• Catalytic/enzyme-binding site is on the inside.

Activation Process:

1. Hormone binds to the receptor's extracellular domain.

2. Directly activates an associated enzyme (or inactivates one).
3. Enzyme activity leads to changes in cell function.

Examples:

• Leptin receptor: Member of a cytokine receptor family.

o Lacks intrinsic enzyme activity but signals through JAK2 (Janus
kinase).
o Leptin binding activates JAK2, which phosphorylates STAT proteins.
o STAT proteins trigger gene transcription and protein synthesis.

Overall, this passage highlights the diverse mechanisms by which hormones

interact with their target cells to exert a wide range of physiological effects.
Adrenocorticotropic hormone (ACTH), Angiotensin II, Calcitonin, Catecholamines
(acting on beta receptors), Corticotropin-releasing hormone (CRH), Follicle-
stimulating hormone (FSH), Glucagon, Growth hormone-releasing hormone (GHRH),
Human chorionic gonadotropin (hCG), Luteinizing hormone (LH), Parathyroid
hormone (PTH), Secretin, Somatostatin, Thyroid-stimulating hormone (TSH), and
Vasopressin (acting on V2 receptors in epithelial cells) are all hormones that play
crucial roles in regulating various physiological processes in the body. Here's a
detailed summary of their functions and mechanisms of action:

1. Adrenocorticotropic Hormone (ACTH): ACTH is produced by the anterior pituitary

gland and stimulates the adrenal cortex to secrete cortisol, which is involved in the
body's response to stress and helps regulate metabolism, immune function, and
blood pressure.

2. Angiotensin II: Angiotensin II is a hormone that constricts blood vessels,

increasing blood pressure. It also stimulates the release of aldosterone from the
adrenal glands, which helps regulate blood volume and pressure.

3. Calcitonin: Calcitonin is produced by the thyroid gland and helps regulate calcium
levels in the blood by inhibiting the breakdown of bone and promoting calcium
excretion by the kidneys.

4. Catecholamines (acting on beta receptors): Catecholamines, such as adrenaline

and noradrenaline, act on beta receptors to increase heart rate, dilate airways, and
mobilize energy stores in response to stress or danger.

5. Corticotropin-releasing hormone (CRH): CRH is produced by the hypothalamus

and stimulates the release of ACTH from the pituitary gland, which in turn stimulates
the adrenal glands to produce cortisol.

6. Follicle-stimulating hormone (FSH): FSH is produced by the pituitary gland and

plays a key role in regulating the menstrual cycle and sperm production.

7. Glucagon: Glucagon is produced by the pancreas and helps regulate blood sugar
levels by stimulating the liver to convert glycogen into glucose and release it into the
bloodstream.

8. Growth hormone-releasing hormone (GHRH): GHRH is produced by the

hypothalamus and stimulates the pituitary gland to release growth hormone, which is
important for growth, metabolism, and cell repair.

9. Human chorionic gonadotropin (hCG): hCG is produced by the placenta during

pregnancy and helps maintain the pregnancy by stimulating the ovaries to produce
progesterone.
10. Luteinizing hormone (LH): LH is produced by the pituitary gland and plays a key
role in regulating the menstrual cycle and ovulation in women, and testosterone
production in men.

11. Parathyroid hormone (PTH): PTH is produced by the parathyroid glands and
helps regulate calcium and phosphorus levels in the blood by increasing calcium
absorption in the intestines and releasing calcium from bone.

12. Secretin: Secretin is produced by the small intestine and helps regulate the pH of
the digestive system by stimulating the pancreas to release bicarbonate.

13. Somatostatin: Somatostatin is produced by the hypothalamus and pancreas and

inhibits the release of growth hormone, insulin, and other hormones.

14. Thyroid-stimulating hormone (TSH): TSH is produced by the pituitary gland and
stimulates the thyroid gland to produce thyroid hormones, which regulate
metabolism, growth, and development.

15. Vasopressin (acting on V2 receptors in epithelial cells): Vasopressin, also known

as antidiuretic hormone (ADH), is produced by the hypothalamus and regulates
water balance by increasing water reabsorption in the kidneys.

These hormones exert their effects through various mechanisms, including the
activation of specific receptors on target cells, which then trigger intracellular
signaling pathways leading to the desired physiological responses.
Hormone Signaling and Second Messengers

This passage dives into two main categories of hormone receptors and the signaling
pathways they activate:

Intracellular Hormone Receptors and Gene Activation:

• Liposoluble steroid hormones (adrenal/gonadal), thyroid hormones, retinoid

hormones, and vitamin D belong to this category.
• These hormones can readily cross the cell membrane.
• They bind to protein receptors located inside the cytoplasm or nucleus.
• The hormone-receptor complex then interacts with specific DNA sequences
(hormone response elements) on genes.
• This interaction can either activate or repress transcription of specific genes,
leading to mRNA and protein synthesis.
• The response time for these hormones can range from minutes to days.
• Different tissues may have the same receptors but regulate different genes
upon hormone binding.
• The specific cellular response depends on both receptor presence and the
genes the receptor regulates in that tissue.

Second Messenger Mechanisms:

 • Second messengers are molecules produced inside the cell in response to
hormone binding to cell surface receptors.
• They amplify the hormonal signal and trigger various cellular responses.
• Common second messengers include:
o Cyclic adenosine monophosphate (cAMP)
o Calcium ions (Ca2+) and calmodulin
o Products of membrane phospholipid breakdown

Adenylyl Cyclase-cAMP Second Messenger System:

• This system is used by many hormones (Table 75-3 is mentioned in the

passage but not shown here).
• The process involves these steps:
1. Hormone binds to its receptor.
2. The receptor couples with a stimulatory G protein (Gs protein).
3. Gs protein activates the enzyme adenylyl cyclase in the cell
membrane.
4. Adenylyl cyclase converts ATP into cAMP.
5. cAMP activates protein kinase A (PKA), which phosphorylates various
cellular proteins.
6. Phosphorylated proteins trigger specific cellular responses.
• cAMP often works through a cascade effect, amplifying the signal.
• Inhibitory G proteins (Gi proteins) can inhibit adenylyl cyclase, reducing cAMP
and leading to cellular inhibition.
• The specific cellular response depends on the enzymes and machinery
present in the target cell.
o Examples: Thyroid hormone production in thyroid cells vs. steroid
hormone secretion in adrenocortical cells.

Cell Membrane Phospholipid Second Messenger System:

• Some hormones activate phospholipase C, an enzyme attached to their

receptors.
• Phospholipase C breaks down phosphatidylinositol biphosphate (PIP2) in the
cell membrane into two second messengers:
o Inositol triphosphate (IP3)
o Diacylglycerol (DAG)
• IP3 mobilizes calcium ions from intracellular stores.
• Calcium ions, along with the protein calmodulin, activate various enzymes.
• DAG activates protein kinase C (PKC), which also phosphorylates target
proteins.
• This system leads to diverse cellular responses depending on the cell type.

This passage highlights the intricate mechanisms by which hormones interact with
receptors and utilize second messengers to orchestrate a wide range of cellular
responses.

The summary you provided covers several important hormones and their
mechanisms of action in the body, as well as methods for measuring hormone levels.
Here's a detailed summary of the key points:
1. **Adrenocorticotropic hormone (ACTH)**: Stimulates the adrenal glands to release
cortisol, which is involved in stress response and metabolism.

2. **Angiotensin II**: Acts on epithelial cells to regulate blood pressure and fluid
balance by constricting blood vessels and stimulating aldosterone release.

3. **Calcitonin**: Regulates calcium levels in the blood by inhibiting osteoclast

activity and promoting calcium excretion by the kidneys.

4. **Catecholamines (beta receptors)**: Include hormones like epinephrine and

norepinephrine, which bind to beta receptors to regulate heart rate, blood pressure,
and metabolism.
5. **Corticotropin-releasing hormone (CRH)**: Stimulates the release of ACTH from
the pituitary gland, initiating the stress response.

6. **Follicle-stimulating hormone (FSH)**: Stimulates the growth of ovarian follicles in

females and spermatogenesis in males.

7. **Glucagon**: Increases blood glucose levels by stimulating the liver to convert

glycogen into glucose.

8. **Growth hormone–releasing hormone (GHRH)**: Stimulates the release of

growth hormone from the pituitary gland, which promotes growth and metabolism.

9. **Human chorionic gonadotropin (hCG)**: Produced during pregnancy to maintain

the corpus luteum, which produces progesterone to support the pregnancy.

10. **Luteinizing hormone (LH)**: Stimulates ovulation in females and testosterone

production in males.

11. **Parathyroid hormone (PTH)**: Regulates calcium and phosphate levels in the
blood by stimulating bone resorption and increasing calcium absorption in the
kidneys and intestines.

12. **Secretin**: Stimulates the release of bicarbonate from the pancreas to

neutralize stomach acid.

13. **Somatostatin**: Inhibits the release of growth hormone, insulin, and glucagon.

14. **Thyroid-stimulating hormone (TSH)**: Stimulates the thyroid gland to produce

thyroid hormones, which regulate metabolism.

15. **Vasopressin (V2 receptor, epithelial cells)**: Acts on V2 receptors in epithelial

cells to regulate water reabsorption in the kidneys.

These hormones exert their effects through various mechanisms, including the cAMP
second messenger system, calcium-calmodulin second messenger system, and
direct regulation of gene transcription in the nucleus. Hormone levels can be
measured using sensitive techniques like radioimmunoassay and enzyme-linked
immunosorbent assay (ELISA), which provide accurate and quantitative results
without using radioactive isotopes.

Summary of Hormone Action Mechanisms

This passage discusses three main mechanisms by which hormones exert their
effects on target cells:

1. Second Messenger Systems:

• cAMP Pathway:
o Hormones bind to cell surface receptors.
o Receptor activation can couple with stimulatory G proteins (Gs
proteins) which activate adenylyl cyclase.
o Adenylyl cyclase converts ATP to cAMP, a second messenger.
o cAMP activates protein kinase A (PKA), which phosphorylates various
cellular proteins.
o Phosphorylated proteins trigger specific cellular responses (e.g.,
muscle contraction, secretion).
o Inhibitory G proteins (Gi proteins) can inhibit adenylyl cyclase, reducing
cAMP and leading to cellular inhibition. (Figure 75-7)
o Examples of hormones using cAMP: listed in Table 75-3 (not shown
here).
• Phospholipid Second Messenger Pathway:
o Hormones activate receptors that link to phospholipase C, an enzyme
in the cell membrane.
o Phospholipase C breaks down PIP2 into two second messengers:
inositol triphosphate (IP3) and diacylglycerol (DAG).
o IP3 mobilizes calcium ions from intracellular stores.
o Calcium, with calmodulin, activates various enzymes.
o DAG activates protein kinase C (PKC), which also phosphorylates
target proteins.
o This system leads to diverse cellular responses depending on the cell
type. (Figure 75-8)
o Examples of hormones using phospholipid messengers: listed in Table
75-4 (not shown here).

2. Gene Activation by Intracellular Hormone Receptors:

• Liposoluble steroid hormones (e.g., adrenal/gonadal hormones), thyroid

hormones, and vitamin D can enter cells directly.
• They bind to specific receptor proteins located in the cytoplasm or nucleus.
• The hormone-receptor complex interacts with DNA, regulating transcription of
specific genes.
• This leads to mRNA and protein synthesis, affecting cellular function after
some time (minutes to days).
• The response depends on the genes regulated by the receptor in each tissue
type. (Figure 75-6)
Hormone Measurement Techniques

This passage describes two main methods for measuring hormone concentrations in
blood, which were previously difficult to measure due to their low quantities.

1. Radioimmunoassay (RIA):

• Developed in 1959, revolutionized hormone measurement.

• Requires a highly specific antibody for the target hormone.
• Steps:
o Mix sample fluid with:
▪ Radioactive "standard hormone" (tagged with a radioactive
isotope)
▪ Antibody
o There's limited antibody, so hormone in the sample competes with the
standard hormone for binding sites.
o More radioactive hormone bound by the antibody indicates less natural
hormone in the sample (less competition).
o Conversely, less radioactive hormone bound indicates more natural
hormone (more competition).
o Standard solutions with known hormone concentrations are also run to
create a standard curve.
• Measurement:
o After competition reaches equilibrium, the antibody-hormone complex
is separated, and the radioactivity is measured.
o The amount of radioactive hormone bound is inversely proportional to
the amount of natural hormone in the sample.
o Standard curve allows quantification by comparing the radioactivity of
the unknown sample to the standard curve.
• Sensitivity:
o Can detect hormone levels as low as trillionths of a gram.

2. Enzyme-Linked Immunosorbent Assay (ELISA):

• More recent method, gaining popularity.

• Advantages:
o Doesn't use radioactive isotopes (safer).
o Can be automated (faster and more efficient).
o Cost-effective.
• Principle:
o Uses the specificity of antibodies and the sensitivity of enzyme assays.
o Performed on plates with multiple wells.
o Each well is coated with an antibody specific for the target hormone.
o Samples or standards are added, followed by a second antibody that
also binds the hormone at a different site.
o A third antibody linked to an enzyme is then added.
o This third antibody recognizes the second antibody.
o The enzyme converts a substrate into a detectable product (colored or
fluorescent).
 oMore hormone leads to more antibody-hormone complexes, leading to
more enzyme and more product formation.
• Measurement:
o The amount of product formed is proportional to the amount of
hormone present.
o Higher product levels indicate higher hormone concentrations.

Overall:

Both RIA and ELISA are highly sensitive techniques that allow for accurate
measurement of very low hormone concentrations in blood samples. ELISA offers
advantages in terms of safety, automation, and cost, making it a popular choice in
clinical and research settings.

Answer the following questions:

1. **Neurotransmitters**: These are chemical messengers that transmit signals

across a synapse from one neuron (nerve cell) to another target neuron, muscle cell,
or gland cell. Neurotransmitters are released from synaptic vesicles in response to a
nerve impulse and bind to specific receptors on the target cell, triggering a response.
Examples include dopamine, serotonin, and acetylcholine.

**Neuroendocrine hormones**: These are hormones produced by neurosecretory

cells, which are specialized neurons that release hormones into the bloodstream.
These hormones are synthesized in the hypothalamus and released from the
posterior pituitary gland. Examples include oxytocin and vasopressin.

**Endocrine hormones**: These are chemical messengers secreted by endocrine

glands directly into the bloodstream. They travel throughout the body to target
tissues where they exert their effects. Examples include insulin, cortisol, and thyroid
hormones.

**Paracrine hormones**: These are chemical messengers that act locally on

neighboring cells. They are secreted by a variety of cells and regulate the function of
nearby cells without entering the bloodstream. Examples include histamine and
prostaglandins.

**Autocrine hormones**: These are chemical messengers that act on the same cell
that secretes them, leading to self-regulation. They bind to receptors on the surface
of the secreting cell, influencing its own function or activity. Examples include
interleukins and growth factors.

2. **Hormone classes**:

- Protein/Peptide Hormones: Examples include insulin (pancreas), growth hormone

(pituitary gland), and parathyroid hormone (parathyroid glands).

- Amine Hormones: Examples include adrenaline (adrenal medulla), noradrenaline

(adrenal medulla), and thyroxine (thyroid gland).

- Steroid Hormones: Examples include cortisol (adrenal cortex), androgen (testes,

ovaries), and estrogen (ovaries).

3. **Protein hormone synthesis and secretion**:

- **Synthesis**: Preprohormones are synthesized in the rough endoplasmic reticulum

(RER) and then cleaved to prohormones in the Golgi apparatus. Prohormones are
packaged into secretory vesicles.

- **Secretion**: When the cell receives a signal, the secretory vesicles move to the
cell membrane and release their contents (prohormones), which are then cleaved to
active hormones.

4. **Steroid hormone synthesis and secretion**:

- **Synthesis**: Steroid hormones are derived from cholesterol and are synthesized
in the smooth endoplasmic reticulum (SER) and mitochondria of steroidogenic cells.

- **Secretion**: Once synthesized, steroid hormones diffuse out of the steroidogenic

cells into the bloodstream because they are lipid-soluble.

5. **Thyroid hormones synthesis and secretion**:

- **Synthesis**: Thyroid hormones are synthesized from tyrosine and iodine within
the thyroid follicles. Thyroglobulin is synthesized in the thyroid cells and contains the
precursor molecules for thyroid hormones.

- **Secretion**: Thyroid hormones are stored in the colloid within thyroid follicles and
are released into the bloodstream when thyroid cells are stimulated by thyroid-
stimulating hormone (TSH) from the pituitary gland.

6. **Transport of hormones in the blood**:

- **Water-soluble hormones**: These hormones are transported dissolved in the
plasma, as they are hydrophilic and cannot pass through the lipid bilayer of cell
membranes. Examples include peptide hormones and catecholamines.

- **Lipid-soluble hormones**: These hormones bind to carrier proteins in the blood,

such as albumin and globulins, to increase their solubility and protect them from
degradation. Examples include steroid hormones and thyroid hormones.

7. **Receptor location and hormone type**:

- **Cell membrane receptors**: These receptors are found on the cell surface and
are activated by water-soluble hormones, including protein/peptide hormones and
catecholamines.

- **Intracellular receptors**: These receptors are located inside the cell and are
activated by lipid-soluble hormones, including steroid hormones and thyroid
hormones.

8. **Three types of cell membrane receptors**:

- **G protein-coupled receptors (GPCRs)**: Bind to hormones like adrenaline and
glucagon.

- **Ion channel-linked receptors**: Bind to neurotransmitters like acetylcholine.

- **Enzyme-linked receptors**: Bind to growth factors and cytokines.

9. **Second messenger mechanisms activated by G-protein-linked receptors**:

- **cAMP second messenger system**: Activated by hormones like adrenaline and

glucagon.

- **Phospholipase C second messenger system**: Activated by hormones like

angiotensin II and gonadotropin-releasing hormone (GnRH).

10. **Intracellular receptors for lipid-soluble hormones**:

- **Cytoplasmic receptors**: Bind to hormones like steroid hormones.

- **Nuclear receptors**: Bind to hormones like thyroid hormones.

11. **Feedback control**:

- **Positive feedback**: Amplifies the response. An example is the release of
oxytocin during childbirth, which stimulates further contractions.

- **Negative feedback**: Reduces the response. An example is the release of insulin

in response to high blood glucose levels, which lowers blood glucose levels.

12. **Clearance of hormones from the blood**:

- **Metabolism**: Hormones can be broken down by enzymes in the liver and other
tissues.

- **Excretion**: Hormones and their metabolites can be excreted in urine or bile.

- **Binding to receptors**: Hormones can bind to receptors on target cells, reducing

their concentration in the blood.

- **Diffusion**: Hormones can diffuse out of the bloodstream into tissues.

13. **Formula for determining hormone clearance rate**:

- Clearance rate = (Rate of hormone removal from blood) / (Concentration of
hormone in blood).

14. **Half-life of a hormone**:

- The half-life of a hormone is the time it takes for half of the hormone to

be cleared from the bloodstream.

15. **Difference in half-life between peptide/catecholamine and thyroid hormones**:

- Peptide and catecholamine hormones have shorter half-lives (minutes to hours)

due to rapid metabolism and excretion.

- Thyroid hormones have longer half-lives (days) due to slower metabolism and
clearance.

Study Unit 2
• Pituitary secretion is primarily controlled by hormonal or nervous signals from
the hypothalamus, with most secretion controlled by hypothalamic releasing
and inhibitory hormones.
• The hypothalamus also receives signals from various sources in the nervous
system and integrates information to control pituitary hormone secretion.
• The anterior pituitary is highly vascular, and almost all the blood that enters its
sinuses passes through a capillary bed in the lower hypothalamus via
hypothalamic-hypophysial portal blood vessels.
• Hypothalamic releasing and inhibitory hormones are secreted into the median
eminence and tuber cinereum, and they control the secretion of anterior
pituitary hormones.
• Specific areas in the hypothalamus control the secretion of specific
hypothalamic-releasing and inhibitory hormones, which are then transported
to the anterior pituitary gland to regulate hormone secretion.
• All major anterior pituitary hormones, except GH, primarily stimulate target
glands (thyroid, adrenal cortex, ovaries, testicles, mammary glands).
• GH acts directly on almost all tissues of the body, promoting growth.
• GH, also known as somatotropic hormone or somatotropin, is a small protein
molecule with 191 amino acids, promoting growth of almost all body tissues.
• GH enhances cell size, mitosis, and differentiation of certain cell types, such
as bone and muscle cells.
• GH has metabolic effects, including increased protein synthesis, mobilization
of fatty acids from adipose tissue, and decreased glucose utilization.
• GH enhances amino acid transport, RNA translation for protein synthesis, and
DNA transcription for increased RNA production.
• GH decreases protein breakdown and enhances fat utilization for energy.
• Excessive GH can cause ketosis and fatty liver due to increased mobilization
of fat.
• GH decreases glucose uptake in tissues, increases glucose production by the
liver, and increases insulin secretion, leading to insulin resistance and
increased blood glucose levels.
• Insulin and carbohydrates are necessary for GH to be effective in promoting
growth.
• GH stimulates bone growth by increasing protein deposition, cell reproduction,
and conversion of chondrocytes to osteogenic cells.
• GH stimulates long bone growth at epiphyseal cartilages and thickens bones
by stimulating osteoblasts.
• GH exerts many of its effects through insulin-like growth factors (IGFs),
especially IGF-1, which mediates some growth and metabolic effects of GH.
• Children with a deficiency of IGF fail to grow normally despite normal or
elevated GH secretion.
• Pygmy peoples of Africa and some other dwarfs (e.g., Laron syndrome) have
small stature due to an inability to synthesize significant amounts of IGF-1,
even though their GH secretion may be normal or high.
• GH's growth effects are mainly mediated by IGF-1 and other IGFs, rather than
directly on bones and tissues.
• GH injection into epiphyseal cartilages of bones causes growth, suggesting
local IGF-1 formation may play a role.
• GH has a short duration of action, rapidly released into tissues with a half-life
of <20 minutes, while IGF-1 has a prolonged action with a half-life of about 20
hours due to strong attachment to carrier proteins in the blood.
• GH secretion decreases slowly with aging, falling to about 25% of adolescent
levels in very old age.
• GH secretion is pulsatile and influenced by factors like starvation,
hypoglycemia, low fatty acid levels, exercise, excitement, trauma, ghrelin, and
certain amino acids, as well as deep sleep.
• GHRH and somatostatin, secreted by the hypothalamus, control GH
secretion, with GHRH stimulating and somatostatin inhibiting GH secretion.
• GH secretion is subject to negative feedback control.
• Adult panhypopituitarism, a decrease in all anterior pituitary hormones, may
result from tumors or thrombosis of pituitary blood vessels, leading to
hypothyroidism, reduced glucocorticoid production, and suppressed
gonadotropic hormones.
• Panhypopituitarism during childhood results in dwarfism, with delayed bodily
development and lack of sexual functions.
• Human Growth Hormone (hGH) is used to treat GH deficiency, synthesized
using recombinant DNA technology.
• Gigantism can occur when there is excessive GH production before
adolescence, causing rapid growth of all body tissues, including bones,
resulting in heights up to 8 feet tall.
• GH Secretion and IGF Deficiency in Growth:
• Children with IGF deficiency fail to grow normally despite normal or
elevated GH secretion.
• Pygmy peoples of Africa have small stature due to an inability to
synthesize significant amounts of IGF-1, despite normal or high GH
levels.
• Other dwarfs (e.g., Laron syndrome) have similar issues due to a
mutation of the GH receptor, leading to failure of GH to stimulate IGF-1
formation.
• Growth effects of GH are largely mediated by IGF-1 and other IGFs,
rather than direct effects on bones and tissues.
• GH can cause local growth by stimulating IGF-1 formation in tissues
like epiphyseal cartilages.
• GH also has IGF-independent effects, stimulating growth in tissues like
chondrocytes.
• Duration of GH Action and Regulation:
• GH attaches weakly to plasma proteins, leading to rapid release into
tissues with a half-time in blood of less than 20 minutes.
• IGF-1 attaches strongly to a carrier protein, released slowly with a half-
time of about 20 hours.
• GH secretion decreases with age, falling to about 25% of adolescent
levels in very old age.
• GH secretion is pulsatile, influenced by factors like nutrition, stress,
exercise, excitement, trauma, ghrelin, and certain amino acids.
• GH increases during the first 2 hours of deep sleep.
• Normal plasma GH concentrations are between 1.6-3 ng/ml in adults
and about 6 ng/ml in children or adolescents.
• Regulation of GH Secretion:
• Factors like starvation, hypoglycemia, low fatty acids, exercise,
excitement, trauma, ghrelin, and certain amino acids stimulate GH
secretion.
 •
GH secretion correlates with cellular protein depletion more than
glucose insufficiency in chronic conditions.
• Severe protein malnutrition causes excess GH production, corrected
only by protein supplementation.
• GH secretion is controlled by GHRH and somatostatin secreted by the
hypothalamus.
• GHRH stimulates GH secretion through cell membrane receptors,
activating the adenylyl cyclase system.
• GH secretion is subject to negative feedback control.
• Abnormalities of GH Secretion:
• Panhypopituitarism leads to decreased secretion of all anterior pituitary
hormones, often resulting from pituitary tumors.
• Panhypopituitarism in adults results in hypothyroidism, reduced
glucocorticoid production, and suppressed gonadotropic hormones.
• Most cases of dwarfism result from panhypopituitarism during
childhood, causing delayed bodily development.
• Gigantism results from excessive GH production before epiphyseal
fusion, while acromegaly occurs after fusion, causing bone thickening
and tissue enlargement.
• Aging effects may be related to decreased GH secretion, with studies
showing benefits and risks of GH therapy in older individuals.
• Posterior Pituitary Gland and its Hormones:
• The posterior pituitary gland is composed mainly of glial-like cells
called pituicytes and nerve fibers from the hypothalamus.
• Oxytocin and ADH (vasopressin) are released from nerve endings in
response to nerve impulses.
• ADH regulates water reabsorption in the kidneys by acting on
aquaporins.
• ADH secretion is stimulated by increased extracellular fluid osmolarity,
low blood volume, and low blood pressure.
• Oxytocin stimulates uterine contractions during labor and milk ejection
from the breasts during lactation.

The Pituitary Gland

• Location and Size: A tiny gland (1 cm diameter) situated in a bony cavity

(sella turcica) at the base of the brain.
• Connection to Hypothalamus: Linked to the hypothalamus by a stalk (pituitary
stalk), which facilitates communication and hormone transport.

Divisions:

• Anterior Pituitary (Adenohypophysis):

o Origin: Develops from pharyngeal epithelium, explaining its glandular
structure.
o Major Hormones:
▪ Growth Hormone (GH)
▪ Adrenocorticotropic Hormone (ACTH)
▪ Thyroid-Stimulating Hormone (TSH)
▪ Prolactin (PRL)
 ▪ Follicle-Stimulating Hormone (FSH)
▪ Luteinizing Hormone (LH)
• Posterior Pituitary (Neurohypophysis):
o Origin: Outgrowth of neural tissue from the hypothalamus, hence the
abundance of glial cells (like those found in the nervous system).
o Major Hormones:
▪ Antidiuretic Hormone (ADH/Vasopressin)
▪ Oxytocin

Anterior Pituitary Hormones

• Types of Cells: Each major hormone has a dedicated cell type for synthesis:
o Somatotropes (GH)
o Corticotropes (ACTH)
o Thyrotropes (TSH)
o Gonadotropes (FSH & LH)
o Lactotropes (PRL)
• Hypothalamic Control:
o The hypothalamus secretes releasing and inhibitory hormones into the
hypothalamic-hypophysial portal blood vessels - a direct link between
the hypothalamus and pituitary.
o These hormones then regulate the secretion of the pituitary hormones.

Posterior Pituitary Hormones

• Unique Mechanism:
o Hormones are synthesized in neuron cell bodies in the hypothalamus
(supraoptic and paraventricular nuclei).
o Travel down nerve fibers to be stored and then released from the
posterior pituitary.

Key Points to Remember

• The pituitary's function is heavily influenced by signals it receives from the

hypothalamus, showcasing the close integration between the brain and
endocrine system.
• This tiny gland produces hormones that have extensive control over
metabolism, growth, reproduction, and fluid balance.

Growth Hormone (GH)

• Protein Synthesis: GH strongly enhances protein creation in cells while

reducing protein breakdown. This results in increased tissue growth.
• Fat Utilization: GH drives the body to burn fat for energy, decreasing fat
stores and leading to leaner body mass.
• Carbohydrate Metabolism: GH decreases how readily cells use
carbohydrates for energy. This can sometimes lead to a diabetes-like state,
especially if GH levels are very high.
 • Insulin Connection: To be fully effective, GH needs insulin present. Insulin
assists with the transport of amino acids into cells, which is essential for
increased protein synthesis.

Bone Growth

GH is the major driver of bone growth during childhood and adolescence.

• Long Bones: Promotes lengthening by stimulating activity at the epiphyseal

cartilage (growth plates). Cartilage becomes new bone, lengthening the shaft.
Plates fuse in late adolescence, halting additional length growth.
• Thick Bones: GH stimulates bone-building cells (osteoblasts) throughout life,
leading to thicker bones. This is especially noticeable in the skull and jaw.

Insulin-Like Growth Factors (IGFs/Somatomedins)

• GH causes the liver (and some other tissues) to make IGFs.

• IGFs are the key mediators for many of the growth and metabolic effects we
attribute to GH.
• The most important IGF is IGF-1. Its blood level mirrors GH secretion rate.

Overall Summary

• The pituitary gland is physically divided into anterior (front) and posterior
(rear) parts, which function differently.
• The posterior section only stores hormones. It releases hormones made by
the hypothalamus (a brain area), primarily ADH and oxytocin.
• The anterior section makes and secretes its own hormones. Growth Hormone
(GH) is a major one. Excess or deficiency of GH leads to physical
abnormalities.

Gigantism

• Cause: Pituitary tumor causes excess GH.

• Effects in children and teens (bone growth plates open):
o Excessive height growth due to long bones getting longer.
o Enlarged hands, feet, facial bones, and some organs.
• Effects overall:
o If untreated, the tumor eventually destroys healthy pituitary tissue,
causing life-shortening hormone deficiencies.
• Treatment: Tumor removal, irradiation therapy

Acromegaly

• Cause: Same as gigantism, but occurs in adults (bone growth plates closed)
• Effects:
o Bones thicken rather than lengthen (especially hands, feet, face).
o Organs may enlarge.
o Hunched back may develop.
Growth Hormone and Aging

• Observation: GH levels decline significantly with age, sometimes correlated

to signs of aging.
• Implication: GH replacement therapy might help some symptoms of aging in
older adults.
• Caveats:
o Can cause serious side effects (diabetes, swelling, pain).
o Therapy is NOT generally recommended for healthy older adults.

Posterior Pituitary

• Structure: Primarily glial cells (pituicytes) and nerve endings from the
hypothalamus.
• Function: Hormone storage and release site, but doesn't make its own
hormones.

Antidiuretic Hormone (ADH, a.k.a. Vasopressin)

• Function: Regulates body water balance

o High ADH causes kidneys to reabsorb water, preventing excess urine
output.
o Low ADH makes urine more dilute.
• Regulation:
o Osmoreceptors in hypothalamus: trigger ADH release when body fluids
are too concentrated.
o Baroreceptors (blood pressure sensors): Low blood pressure
stimulates ADH.
• Note: In VERY high concentrations, ADH constricts blood vessels (hence the
name vasopressin).

Oxytocin

• Functions
o Stimulates uterine contractions in childbirth.
o Causes milk release from breasts during breastfeeding.
• Regulation: Triggered by suckling.

Gigantism

• Cause: Pituitary gland tumor that continues to grow, leading to excess growth
hormone (GH).
• Effects:
o Cannot grow taller after adolescence due to fused growth plates, but
bones get thicker and soft tissues grow.
o Enlarged hands, feet, facial bones (especially jaw, forehead, etc.), and
some internal organs like the tongue, kidneys, and liver.
o May develop diabetes.
o Often leads to panhypopituitarism (general pituitary hormone
deficiency), causing early death.
 • Treatment: Microsurgery to remove the pituitary tumor, or irradiation of the
gland to stop tumor growth.

Acromegaly

• Cause: Same as gigantism, but occurs after adolescence (post growth plate
fusion).
• Effects:
o Bones thicken rather than lengthen, leading to enlarged hands, feet,
and facial features.
o May have hunched back (kyphosis) due to vertebral changes.
o Internal organs often enlarge.

Aging and Growth Hormone

• Observation: GH levels naturally decline significantly with age, sometimes

leading to physical changes that look like accelerated aging (wrinkles,
decreased muscle mass, increased fat, loss of energy).
• Potential Implication: Some studies suggest GH replacement in older adults
could help with these symptoms of aging.
• Important Caveats: This therapy can have serious side effects like diabetes,
swelling, joint pain, insulin resistance. It is not generally recommended for
healthy older individuals.

Posterior Pituitary Gland

• Components: Doesn't produce hormones itself. Made of pituicytes (support

cells) and nerve endings from neurons based in the hypothalamus.
• Function: Nerve endings release two hormones made by the hypothalamus:
Antidiuretic hormone (ADH, aka vasopressin) and Oxytocin.

Antidiuretic Hormone (ADH)

• Function: Helps regulate water balance in the body.

o High ADH makes kidney tubules permeable to water, preventing
excessive water loss in the urine.
o Low ADH makes the kidney retain less water, making urine more
dilute.
• Regulation:
o Osmoreceptors in the hypothalamus signal for ADH release when body
fluids get too concentrated.
o Baroreceptors (blood pressure sensors) in major blood vessels also
influence release - low blood volume/pressure increases ADH.
• Additional Note: Very high ADH concentrations cause constriction of blood
vessels, hence the other name, vasopressin.

Oxytocin

• Functions:
 o Stimulates uterine contractions during childbirth, helping the birth
process.
o Causes milk ejection from the breasts during breastfeeding.
• Regulation: Reflexive release triggered by suckling.

Delving Deeper into the Pituitary Gland and its Relationship with the
Hypothalamus:

1. The Symphony of Hormone Production:

• Anterior Pituitary: Imagine the anterior pituitary as an orchestra, with each

cell type acting as a unique instrument. The hypothalamus acts as the
conductor, sending specific "sheet music" (releasing or inhibitory hormones)
through the portal blood vessels. This "music" tells the instruments (cells)
when and how much to play (secrete hormones).
o Positive Reinforcement (Releasing Hormones): When the
hypothalamus sends a releasing hormone (e.g., TRH for TSH), it's like
giving a specific instrument section the sheet music and instructing
them to play. This stimulates the targeted cell type (e.g., thyrotropes) to
increase production and release of their respective hormone (TSH in
this case).
o Negative Reinforcement (Inhibitory Hormones): Conversely, an
inhibitory hormone (e.g., PIH for prolactin) acts like the conductor
telling a section to stop playing or play more softly. This suppresses the
targeted cell type's hormone production.
• Posterior Pituitary: In contrast, the posterior pituitary functions more like a
relay station. The hypothalamus manufactures the hormones (oxytocin and
vasopressin) but stores them in the posterior pituitary. When the
hypothalamus sends nerve signals, they travel down neuronal pathways to
trigger the release of these stored hormones from the posterior pituitary.

2. The Intricate Dance of Feedback Loops:

The communication between the hypothalamus, pituitary, and target organs is not a
one-way street. It's a complex feedback loop, ensuring hormonal balance is
maintained:

• Positive Feedback: In some cases, the released hormone from the pituitary
can stimulate the hypothalamus to increase production of the corresponding
releasing hormone. This can be seen in the surge of LH that triggers
ovulation, leading to further LH release.
• Negative Feedback: More commonly, the released hormone from the
pituitary acts on its target organ, leading to the production of another hormone
that feeds back and inhibits the hypothalamus from releasing the
corresponding releasing hormone. For instance, high levels of thyroid
hormone (produced due to TSH) signal the hypothalamus to decrease TRH
production, thereby regulating thyroid hormone levels.

3. The Maestro of the Endocrine Orchestra:

The pituitary, despite its small size, plays a crucial role in coordinating various
physiological processes through its hormonal influence. Here's a glimpse into some
of its key functions:

• Growth and Development: Growth hormone (GH) from the anterior pituitary
is essential for linear growth during childhood and adolescence, as well as
tissue repair and maintenance throughout life.
• Metabolism: GH also influences carbohydrate, protein, and fat metabolism.
ACTH stimulates the adrenal glands to release cortisol, a hormone involved in
stress response, blood sugar regulation, and immune function.
• Reproduction: FSH and LH regulate the development of eggs in females and
sperm production in males. Prolactin is crucial for milk production in mothers.
• Fluid Balance: The posterior pituitary releases vasopressin, which helps
regulate water reabsorption by the kidneys and maintain blood pressure.
Oxytocin plays a role in childbirth, lactation, and social bonding.

4. Understanding Dysfunction:

Disruptions in the intricate communication between the hypothalamus and pituitary

can lead to various hormonal imbalances and health issues. Some examples
include:

• Pituitary tumors: These can cause either excessive or insufficient hormone

production.
• Hypopituitarism: This occurs when the pituitary fails to produce enough of
one or more hormones.
• Hyperpituitarism: This is the opposite, where the pituitary produces
excessive amounts of one or more hormones.

Answer the following questions

Certainly! Here's a detailed summary, structured to address the key points of the
question:

### Functional Anatomy of the Hypothalamus, Anterior and Posterior Pituitary

Glands:

1. **Hypothalamus:**

- Located above the pituitary gland, it synthesizes and releases hormones that
control the pituitary gland.

- Contains nuclei that produce releasing and inhibiting hormones.

- Synthesizes and secretes oxytocin and vasopressin, which are transported to the
posterior pituitary for storage and release.

2. **Anterior Pituitary Gland (Adenohypophysis):**

- Also known as the adenohypophysis.

- Synthesizes and releases tropic hormones that regulate other endocrine glands.

- Controlled by hypothalamic releasing and inhibiting hormones.

- Hormones produced include GH, TSH, ACTH, FSH, LH, and prolactin.

3. **Posterior Pituitary Gland (Neurohypophysis):**

- Also known as the neurohypophysis.

- Stores and releases oxytocin and vasopressin produced by the hypothalamus.

- Hormones are transported down axons from the hypothalamus to the posterior
pituitary for storage and release.

### Growth Hormone (GH):

a) **Hypothalamic Control:**
- The hypothalamus synthesizes and releases growth hormone-releasing hormone
(GHRH).
- GHRH is transported through the hypophyseal portal system to the anterior pituitary
gland.

- GHRH stimulates the synthesis and secretion of GH from somatotropic cells in the
anterior pituitary.

b) **Synthesis and Secretion:**

- GH is a protein hormone synthesized from amino acids.

- Somatotropic cells in the anterior pituitary gland produce and release GH in
response to GHRH.

- GH is released in a pulsatile manner, influenced by various factors.

c) **Transport:**

- GH is a water-soluble hormone.

- It is transported in the blood bound to GH-binding proteins.

d) **Target Tissue:**

- GH binds to GH receptors on target cells, primarily in the liver.

- This binding activates the JAK-STAT signaling pathway, leading to the production of
insulin-like growth factor 1 (IGF-1).

### Oxytocin:

a) **Hypothalamic Control:**
- Oxytocin is synthesized in the paraventricular nucleus and supraoptic nucleus of
the hypothalamus.
- It is transported to the posterior pituitary for storage and release.

b) **Transport:**

- Oxytocin is a peptide hormone and is water-soluble.

- It is transported in the blood to target tissues.

c) **Target Tissue:**

- Oxytocin acts on the uterus during labor to stimulate contractions.

- It also acts on the mammary glands to stimulate milk ejection during breastfeeding.
### Summary Table:

Aspect Growth Hormone (GH) Oxytocin

Hypothalamic GHRH stimulates GH release from Produced in hypothalamus,
Control anterior pituitary stored in PP
Synthesis and Synthesized in anterior pituitary from
Secretion amino acids Synthesized in hypothalamus
Water-soluble, transported in blood Water-soluble, transported in
Transport bound to proteins blood
Binds to liver cells, stimulates IGF-1 Acts on uterus and mammary
Target Tissue production glands
| **Hypothalamic Control** | GHRH stimulates GH release from anterior pituitary
| Produced in hypothalamus, stored in PP |

| **Synthesis and Secretion** | Synthesized in anterior pituitary from amino acids

| Synthesized in hypothalamus |
| **Transport** | Water-soluble, transported in blood bound to proteins |
Water-soluble, transported in blood |
| **Target Tissue** | Binds to liver cells, stimulates IGF-1 production |
Acts on uterus and mammary glands |

### Other Names:

- **Anterior Pituitary Gland:** Adenohypophysis

- **Posterior Pituitary Gland:** Neurohypophysis

- **Growth Hormone (GH):** Somatotropin

- **Somatomedin C:** Insulin-like Growth Factor 1 (IGF-1)

### Physiological Functions of GH:

1. Stimulates growth and development of bones and tissues.

2. Promotes protein synthesis and inhibits protein breakdown.

3. Stimulates lipolysis, mobilizing fatty acids for energy.

4. Increases blood glucose levels through gluconeogenesis.

### Metabolic Effects of GH (excluding bone growth):

1. Increases protein synthesis and inhibits protein breakdown.

2. Stimulates lipolysis, releasing fatty acids.

3. Increases blood glucose levels through gluconeogenesis.

### Ketogenic Effect of Excessive GH:

- Excessive GH can lead to increased breakdown of fatty acids, producing ketones,
which can be used as an energy source.

### Relationship between GH and Somatomedin C (IGF-1):

- GH stimulates the liver to produce IGF-1, which mediates many of the growth-
promoting effects of GH.

### Variations in GH Secretion:

- **With an increase in age:** GH secretion decreases.
- **During strenuous exercise:** GH secretion increases.

- **During sleep:** GH secretion increases, particularly during deep sleep.

### ADH Secretion in Response to Decreased Blood Volume and Pressure:

a) **Increase or Decrease:** ADH secretion will increase.

b) **Physiological Effect on Kidneys:** Increases water reabsorption, reducing urine
output.

c) **Physiological Effect on Arterioles:** Causes vasoconstriction, increasing blood

pressure.

### Influence of Alcohol on ADH Secretion:

- Drinking alcohol inhibits ADH secretion, leading to increased urine output and
potentially dehydration.

### Physiological Effect of Oxytocin on the Uterus during Labour:

- Oxytocin stimulates uterine contractions, aiding in the progression of labor and

childbirth.

### Physiological Effect of Oxytocin on the Mammary Glands during Breastfeeding:

- Oxytocin stimulates the contraction of myoepithelial cells around the mammary

gland alveoli, facilitating milk ejection.

### Possible Function of Oxytocin in Males:

- Oxytocin may play a role in sexual arousal and orgasm in males, as well as in
social bonding and behavior.

Functional Anatomy of the Hypothalamus, Anterior & Posterior Pituitary Gland:

Hypothalamus: Located at the base of the brain, the hypothalamus is responsible

for various functions, including hormone regulation. It synthesizes releasing
hormones (RHs) that travel to the anterior pituitary via the hypophyseal portal
system.

Anterior Pituitary Gland (Adenohypophysis): Also known as the frontal lobe of

the pituitary gland, it synthesizes and secretes hormones based on the releasing
hormones received from the hypothalamus. These hormones are:

• Growth hormone (GH)

• Thyroid-stimulating hormone (TSH)
• Prolactin
• Follicle-stimulating hormone (FSH)
 • Luteinizing hormone (LH)
• Adrenocorticotropic hormone (ACTH)

Posterior Pituitary Gland (Neurohypophysis): Also known as the neural lobe of

the pituitary gland, it stores and releases hormones synthesized in the
hypothalamus:

• Oxytocin
• Antidiuretic hormone (ADH) or Vasopressin
Growth Hormone (GH)

a) Hypothalamic Control: The hypothalamus synthesizes growth hormone-

releasing hormone (GHRH), which travels to the anterior pituitary via the
hypophyseal portal system. GHRH binds to GHRH receptors on somatotrophs,
stimulating GH synthesis and secretion.

b) Synthesis and Secretion: GH is a protein hormone synthesized by

somatotrophs in the anterior pituitary. Secretion is pulsatile and influenced by
various factors (discussed later).

c) Transport: GH is a protein hormone and is water-soluble. Hence, it travels

freely dissolved in the blood to target tissues.

d) Target Tissue and Action: GH binds to GH receptors on various tissues,

including:

• Liver: Stimulates the production of insulin-like growth factor 1 (IGF-1), also

known as somatomedin C, which mediates most of GH's effects.
• Bone: Stimulates chondrocyte proliferation and bone growth.
• Muscle: Increases protein synthesis and muscle growth.
• Adipose tissue: Increases lipolysis (fat breakdown).

GH and Somatomedin C: GH stimulates the liver to produce somatomedin C, which

acts on target tissues to exert most of GH's physiological functions.

GH Secretion Variations:

• Age: Decreases with age.

• Exercise: Increases during strenuous exercise.
• Sleep: Increases during deep sleep stages.
Oxytocin

a) Hypothalamic Control: The supraoptic nucleus and paraventricular nucleus

of the hypothalamus synthesize oxytocin. These nuclei are neurosecretory and
their axons extend to the posterior pituitary for storage and release.

b) Transport: Oxytocin is a peptide hormone and is water-soluble. Hence, it

travels freely dissolved in the blood to target tissues.
c) Target Tissue and Action: Oxytocin binds to oxytocin receptors on various
tissues, including:

• Uterus: Stimulates uterine contractions during labor.

• Mammary glands: Stimulates milk ejection during breastfeeding.
• Brain: May play a role in social bonding, sexual behavior, and anxiety.
Other Information:

• Another name for Growth Hormone (GH) is Somatropin.

• Another name for Somatomedin C is IGF-1.
• Physiological functions of GH:
o Stimulates linear growth (bone growth).
o Increases muscle mass and strength.
o Promotes fat metabolism.
o Maintains normal blood sugar levels.
• Metabolic effects of GH (excluding bone growth):
o Increases lipolysis (fat breakdown).
o Promotes glucose uptake by cells.
o Inhibits glucose production by the liver.
• The ketogenic effect of excessive GH: Excessive GH can lead to increased
lipolysis, resulting in the production of ketone bodies from fatty acids, which
can be harmful in high amounts.
• ADH secretion decreases when blood volume and blood pressure decrease.
This decrease signals the kidneys to excrete less water, conserving blood
volume and raising blood pressure.
• ADH constricts arterioles, further increasing blood pressure.
• Within 5 minutes of drinking wine, ADH secretion decreases due to the
diuretic effect of alcohol, leading to increased urine output.
• Oxytocin stimulates uterine contractions during labor, expelling the baby.
• Oxytocin stimulates milk ejection during breastfeeding, allowing
 Study Unit 3
The Thyroid Gland: Making and Storing Hormones

This passage discusses the thyroid gland and how it produces and stores hormones
crucial for regulating metabolism. Here's a breakdown of the key points:

Iodide Trapping:

• The thyroid gland concentrates iodide (a form of iodine) from the bloodstream
through a pump called the sodium-iodide symporter (NIS).
• TSH, a hormone from the pituitary gland, stimulates this process.

Thyroglobulin and Hormone Formation:

• Thyroid cells create a large protein called thyroglobulin, which stores iodine
atoms.
• An enzyme, peroxidase, oxidizes iodide into a usable form for bonding with
thyroglobulin.
• Iodine binds to specific amino acids (tyrosine) within thyroglobulin molecules.
• This binding process creates monoiodotyrosine (MIT) and diiodotyrosine
(DIT).
• DIT molecules can combine to form thyroxine (T4), the main thyroid hormone.
• Alternatively, DIT can combine with MIT to form triiodothyronine (T3), another
thyroid hormone but present in smaller amounts.
• A small amount of reverse T3 (RT3) is also formed, but it has no known
significant function.

Storage of Thyroid Hormones:

• Thyroglobulin stores a large amount of T4 and some T3 within the follicles of

the thyroid gland.
• This storage allows the thyroid gland to supply the body's needs for months
even if hormone production stops.

Release of Thyroid Hormones:

• Most thyroglobulin stays stored, and hormones are released by cleaving T4

and T3 from the molecule within the thyroid gland itself.
• Protruding finger-like structures (pseudopods) from the thyroid cells engulf
portions of the colloid (fluid containing thyroglobulin) forming vesicles.
• Lysosomes (digestive sacs) in the cell fuse with these vesicles, releasing
enzymes that break down thyroglobulin and liberate free T4 and T3.
• These free hormones then diffuse into the bloodstream.
Deep Dive into Thyroid Hormone Release and Action

This passage delves into the final stages of thyroid hormone release and how they
exert their effects on the body. Here's a breakdown of the key points:
Releasing Iodinated Tyrosine and Recycling Iodine:

• Not all the iodinated tyrosine molecules stored in thyroglobulin become thyroid
hormones (T4 or T3).
• During the breakdown of thyroglobulin to release T4 and T3, these leftover
iodinated tyrosines (MIT and DIT) are also released.
• An enzyme called deiodinase removes iodine from these leftover molecules.
• The retrieved iodine is then recycled within the gland for new hormone
production.
• A congenital deficiency in this enzyme can lead to iodine deficiency.

Secretion Rates and Conversion of T4 to T3:

• The thyroid gland secretes mostly T4 (93%) and a smaller amount of T3 (7%).
• However, in the bloodstream, about half of the T4 is gradually converted to T3
by deiodinase enzymes.
• This means the majority of the hormone affecting tissues is ultimately T3
(around 35 μg daily).

Transporting Thyroid Hormones:

• Once released, over 99% of T4 and T3 bind to plasma proteins in the

blood, mainly thyroxine-binding globulin.
• This binding slows down the delivery of hormones to tissues.
• T4 has a higher affinity for these proteins and is released even slower than T3
(half-life of 6 days vs 1 day).

Cellular Uptake and Action of Thyroid Hormones:

• Both T4 and T3 enter cells and bind to intracellular proteins.

• T4 binds more tightly, acting as a reservoir.
• The binding with proteins delays the hormones' action and allows for a
sustained effect.
• It takes several days for a significant effect on metabolism to be observed
after T4 injection.
• T3 acts more rapidly due to its weaker protein binding.

Thyroid Hormone Effects at the Cellular Level:

• Thyroid hormones primarily work by increasing the transcription of many

genes in the cell nucleus.
• This leads to the production of more proteins with various functions, resulting
in increased cellular activity throughout the body.
• Most secreted T4 is converted to T3 before affecting gene transcription.
• T3 has a higher affinity for the nuclear receptors that trigger gene activation.
• These receptors bind to specific DNA regions and initiate the formation of
messenger RNA (mRNA).
• mRNA then directs the production of new proteins in the cytoplasm.

Non-Genomic Effects:
 • In some cases, thyroid hormones seem to have rapid effects (within minutes)
independent of gene transcription.
• These effects might involve influencing ion channels, energy production
(oxidative phosphorylation) within cells, or other processes.
• The locations for these non-genomic actions include the cell
membrane, cytoplasm, and possibly organelles like mitochondria.

The passage highlights the complex interplay between hormone storage, release,
transport, and cellular action. It emphasizes the crucial role of T3 in influencing gene
expression and overall cellular activity.

The chapter discusses the thyroid metabolic hormones, primarily thyroxine (T4) and
triiodothyronine (T3), and their role in the body. Here's a detailed summary:

**Iodide Trapping:**

- The thyroid gland concentrates iodide from the blood, establishing a low
intracellular sodium concentration to facilitate iodide diffusion into cells.

- Thyroid-stimulating hormone (TSH) influences the rate of iodide trapping, with

higher TSH levels increasing trapping activity.

**Thyroglobulin and Hormone Formation:**

- Thyroid cells synthesize and secrete thyroglobulin, a large glycoprotein that

contains tyrosine amino acids, which bind with iodine to form thyroid hormones.

- Thyroxine (T4) and triiodothyronine (T3) are formed within the thyroglobulin
molecule, which serves as a storage reservoir for these hormones.

- The process of iodination and coupling of tyrosine residues leads to the formation
of T4 and T3, with T4 being the major product.

**Release of Thyroxine and Triiodothyronine:**

- Thyroglobulin is not released directly into the blood; instead, it is cleaved within
thyroid cells to release free T4 and T3.

- The process involves pinocytic vesicles that enter the cell apex, where lysosomes
digest thyroglobulin, releasing T4 and T3 into the blood.

**Transport to Tissues:**
- Thyroxine and T3 bind with plasma proteins upon entering the blood, mainly with
thyroxine binding globulin.
- These bound hormones are released slowly to tissue cells, with half-life times of
about 6 days for T4 and 1 day for T3.

**Physiological Functions:**

- Thyroid hormones activate nuclear transcription of many genes, leading to

increased synthesis of enzymes, structural proteins, and other substances,
enhancing overall body activity.

- Most of the thyroxine secreted by the thyroid is converted to triiodothyronine, which

binds more readily to intracellular receptors and is the active form of the hormone.

- Thyroid hormones also have nongenomic effects, acting rapidly on cellular

functions through mechanisms independent of gene transcription.

**Conclusion:**

- Thyroid hormones play a crucial role in regulating metabolic processes and overall
body functions through their effects on gene transcription and cellular activities.

How Thyroid Hormones Rev Up Your Cells

This passage explains how thyroid hormones influence cellular activity and their
overall impact on the body. Here's a breakdown of the key points:

Cellular Effects:

• Thyroid hormones can activate secondary messengers inside cells, like cyclic
AMP, influencing various processes.
• They significantly increase the basal metabolic rate (BMR), the rate at which
cells burn energy, by up to 100%.
• This leads to faster utilization of food for energy production.
• Protein synthesis increases, but so does protein breakdown.
• In young individuals, growth accelerates.
• Mental processes are stimulated, and other endocrine glands become more
active.

Mitochondria and Energy Production:

• Thyroid hormones can increase the number and activity of mitochondria, the
powerhouses of cells.
• This potentially boosts the production of ATP (cellular fuel) to meet the
heightened energy demands.
• The increased activity could also be a consequence of the overall cellular
stimulation.
Cellular Transport:

• Thyroid hormones enhance the activity of Na+-K+ ATPase, a pump that

moves sodium and potassium ions across cell membranes.
• This process uses energy and generates heat, potentially contributing to the
increased BMR.
• Thyroid hormones might also make cell membranes leakier to sodium, further
activating the pump and heat production.

Growth and Development:

• Thyroid hormone is crucial for tadpole metamorphosis and overall growth in

children.
• Deficiency in children leads to stunted growth, while excess can cause early,
rapid growth with premature bone maturation, ultimately leading to shorter
stature.
• It's vital for brain development during fetal life and early childhood.
• Insufficient thyroid hormone during this period can cause permanent mental
retardation.

Specific Body Functions:

• Carbohydrate Metabolism: Thyroid hormones stimulate various aspects of

carbohydrate metabolism, including:
o Increased glucose uptake by cells
o Enhanced breakdown of glucose (glycolysis)
o Increased production of glucose from non-carbohydrate sources
(gluconeogenesis)
o Faster absorption from the gut
o Increased insulin secretion with its own effects
• Fat Metabolism: Thyroid hormones also enhance fat metabolism:
o They mobilize stored fats, reducing fat stores.
o They increase free fatty acid levels in the blood and their utilization by
cells.
o They decrease blood cholesterol, phospholipids, and triglycerides while
increasing free fatty acids.
o Conversely, low thyroid hormone levels have the opposite effects,
raising bad cholesterol and promoting fat deposition.
o Increased cholesterol excretion in bile could be a mechanism for
lowering blood cholesterol levels.

Deep Dive into the Effects of Thyroid Hormone Throughout the Body

This passage explores the wide-ranging effects of thyroid hormone on various bodily
systems. Here's a breakdown of the key points:

Increased Vitamin Needs:

 • Thyroid hormones increase the production of many enzymes, some requiring
vitamins as components.
• Excess thyroid hormone can lead to a relative vitamin deficiency if intake
doesn't increase.

Basal Metabolic Rate (BMR):

• Thyroid hormone significantly affects BMR, the rate of energy expenditure at

rest.
• High levels can increase BMR by 60-100%, while deficiency reduces it by
half.
• Figure 77-6 illustrates the relationship between thyroid hormone levels and
BMR.

Body Weight:

• Increased thyroid hormone typically leads to weight loss due to the higher
BMR.
• Conversely, low levels often result in weight gain.
• However, appetite can also be affected, potentially countering the metabolic
changes.

Blood Flow and Heart Function:

• Increased metabolism demands more oxygen delivery and waste removal,

leading to vasodilation and increased blood flow, especially to the skin for
heat dissipation.
• Cardiac output (blood pumped by the heart) also rises significantly with high
thyroid hormone levels.
• Heart rate increases more than expected from blood flow increase,
suggesting a direct effect on heart excitability.
• A slight excess can strengthen the heart, but a marked excess weakens it due
to excessive protein breakdown.
• Arterial pressure usually remains normal, but pulse pressure might increase
with higher systolic and lower diastolic values.

Respiration:

• Increased metabolism raises oxygen needs and carbon dioxide production,

stimulating faster and deeper breathing.

Gastrointestinal System:

• Thyroid hormone increases digestive juice secretion and gut motility.

• Hyperthyroidism often leads to diarrhea, while hypothyroidism can cause
constipation.

Central Nervous System:

• Thyroid hormone influences mental processes.

 • High levels lead to faster thinking but potentially disorganized thoughts.
• Low levels slow mental activity.
• Hyperthyroidism can cause nervousness, anxiety, and even paranoia.

Muscles:

• A slight increase in thyroid hormone improves muscle response.

• Excess weakens muscles due to increased protein breakdown.
• Deficiency makes muscles sluggish and slow to relax.

Muscle Tremor:

• A fine, rapid tremor (10-15 times/second) is a characteristic sign of

hyperthyroidism.
• It's believed to be caused by increased nerve cell activity in the spinal cord
areas controlling muscle tone.

Sleep:

• Hyperthyroidism can cause tiredness but difficulty sleeping due to nervous

system stimulation.
• Conversely, hypothyroidism leads to excessive sleepiness, sometimes lasting
12-14 hours a day.

Other Endocrine Glands:

• Increased thyroid hormone stimulates the release of hormones from other

glands like the pancreas (insulin) to meet the body's increased metabolic
demands.
• It also affects bone metabolism (discussed later in the chapter).

The passage highlights how thyroid hormone acts as a conductor, influencing the
tempo of various bodily functions, from metabolism and energy expenditure to heart
function, digestion, and the nervous system. It emphasizes the delicate balance
required for optimal health and the significant disruptions caused by either excess or
deficiency of this crucial hormone.

This passage discusses the physiological effects of thyroid hormones, focusing on

their role in increasing cellular metabolic activity and various body functions. Here's a
detailed summary:

**Activation of Intracellular Secondary Messengers:**

- Thyroid hormones, such as T3 and T4, activate intracellular secondary
messengers, including cyclic adenosine monophosphate (cAMP) or protein kinase
signaling cascades.
- These messengers play a role in gene transcription, mRNA synthesis, and the
synthesis of new proteins.

**Increase in Cellular Metabolic Activity:**

- Thyroid hormones increase the metabolic activities of almost all tissues in the body.

- The basal metabolic rate can increase by 60% to 100% when large quantities of
thyroid hormones are secreted, leading to rapid utilization of foods for energy.

- Protein synthesis rate is increased, but so is protein catabolism.

**Effects on Mitochondria:**

- Thyroid hormones increase the number and activity of mitochondria in cells, which
increases the rate of formation of adenosine triphosphate (ATP) to energize cellular
function.

- This increase in mitochondria could be both a cause and a result of increased

cellular activity.

**Increase in Active Transport of Ions:**

- Thyroid hormones increase the activity of enzymes such as Na+-K+ ATPase, which
increases the rate of transport of sodium and potassium ions through cell
membranes.

- This process uses energy and increases heat production in the body, possibly
contributing to the increase in metabolic rate.

**Effects on Growth:**
- Thyroid hormones have both general and specific effects on growth, including
promoting growth and development of the brain during fetal life and the first few
years of postnatal life.

- In children, hypothyroidism can lead to growth retardation, while hyperthyroidism

can cause excessive skeletal growth but may shorten the duration of growth.

**Effects on Carbohydrate and Fat Metabolism:**

- Thyroid hormone stimulates almost all aspects of carbohydrate metabolism,
including glucose uptake, glycolysis, gluconeogenesis, and insulin secretion.
- It also enhances fat metabolism, mobilizing lipids from fat tissue and increasing
oxidation of free fatty acids.

**Effects on Plasma and Liver Fats:**

- Increased thyroid hormone decreases plasma cholesterol, phospholipids, and

triglycerides, partly by increasing cholesterol secretion in bile.

- This effect may be due to increased numbers of low-density lipoprotein receptors

on liver cells, leading to rapid removal of low-density lipoproteins from the plasma.

**Increased Requirement for Vitamins:**

- Thyroid hormone increases the need for vitamins because it increases the
quantities of many bodily enzymes, some of which require vitamins as cofactors.

**Increased Basal Metabolic Rate and Body Weight:**

- Excessive thyroid hormone can increase the basal metabolic rate by 60% to 100%
above normal, leading to decreased body weight.
- Conversely, when no thyroid hormone is produced, the basal metabolic rate falls to
almost one-half of normal, potentially leading to increased body weight.

**Effects on Cardiovascular System:**

- Thyroid hormone increases blood flow and cardiac output, as well as heart rate and
strength.

- It also affects arterial pressure, respiratory rate, gastrointestinal motility, and central
nervous system excitability.

**Muscle Effects:**

- Thyroid hormone can increase muscle reactivity and strength but can also lead to
muscle weakness due to excess protein catabolism.

- A fine muscle tremor is a characteristic sign of hyperthyroidism, believed to be

caused by increased reactivity of neuronal synapses controlling muscle tone.

**Effects on Sleep and Central Nervous System:**

- Hyperthyroidism can cause a feeling of constant tiredness but difficulty sleeping,
while hypothyroidism can lead to extreme somnolence and long periods of sleep.

**Effects on Other Endocrine Glands:**

- Increased thyroid hormone secretion increases the secretion rates of several other
endocrine glands, such as the pancreas for insulin secretion, to meet the increased
metabolic demands.

In summary, thyroid hormones play a crucial role in regulating metabolic processes

and overall body functions, affecting various systems including metabolism, growth,
cardiovascular function, and central nervous system activity.

The Thyroid Gland: A Delicate Balancing Act

This passage delves into the intricate control mechanisms for thyroid hormone
production and its effects on various bodily functions. Here's a breakdown of the key
points:

Effects of Thyroid Hormone on Other Hormones:

• Thyroid hormone increases the need for parathyroid hormone (PTH) for
calcium regulation (discussed later).
• It accelerates the breakdown of adrenal glucocorticoids in the liver, leading to:
o Increased production of ACTH (adrenocorticotropic hormone) from the
pituitary gland.
o Subsequently, increased secretion of glucocorticoids from the adrenal
glands.

Thyroid Hormone and Sexual Function:

• Both excess and deficiency of thyroid hormone can disrupt sexual function in
both men and women.
o In men, low levels can cause decreased libido and impotence, while
high levels might cause impotence.
o In women, it can cause irregular periods, heavy bleeding, or even
amenorrhea (absence of periods).
• The exact mechanisms are unclear, likely involving a combination of:
o Direct metabolic effects on the sex organs.
o Feedback loops with hormones controlling sexual function from the
pituitary gland.

Regulation of Thyroid Hormone Secretion:

• Precise control is crucial for maintaining normal metabolic activity.

 • This is achieved through a feedback loop involving the hypothalamus, pituitary
gland, and thyroid gland.

TSH (Thyroid Stimulating Hormone) from the Pituitary:

• TSH stimulates thyroid hormone release and has several effects on the
thyroid gland:
o Increases breakdown of stored thyroid hormones, releasing them into
the blood.
o Enhances iodide uptake by the thyroid gland.
o Increases the conversion of tyrosine to thyroid hormones.
o Stimulates growth and secretory activity of thyroid cells.
• TSH works through the cAMP signaling pathway inside thyroid cells.

TRH (Thyrotropin-Releasing Hormone) from the Hypothalamus:

• TRH controls TSH secretion from the pituitary.

• It's a tripeptide produced in the hypothalamus and transported to the pituitary
via blood vessels.
• TRH stimulates TSH release by binding to receptors on pituitary cells,
activating a signaling cascade.

Stimulation of TRH and TSH Secretion:

• Cold exposure is a well-known trigger for increased TRH and TSH secretion,
likely to maintain body temperature.
• Leptin, a hormone regulating energy balance, also plays a role.
• Prolonged fasting reduces leptin levels, leading to decreased TRH and TSH
production, ultimately lowering thyroid hormone output.

The passage highlights the complex interplay between the hypothalamus, pituitary
gland, and thyroid gland in maintaining optimal thyroid hormone levels. It
emphasizes the influence of external factors like temperature and internal signals
like leptin on this delicate hormonal balance.

The Feedback Loop of Thyroid Hormone Production

This passage explains how the body regulates thyroid hormone secretion through a
feedback loop involving the hypothalamus, pituitary gland, and thyroid gland. It also
details how certain substances can disrupt this balance.

Normal Regulation:

• The hypothalamus produces TRH (Thyrotropin-Releasing Hormone),

stimulating the pituitary gland to release TSH (Thyroid Stimulating Hormone).
• TSH prompts the thyroid gland to produce thyroid hormones (T3 and T4).
• Increased thyroid hormone levels in the blood suppress TSH secretion from
the pituitary (feedback loop).

Figure 77-7 summarizes this process.

Impact of Emotions:

• Excitement and anxiety can decrease TSH secretion, possibly due to their
opposing effects on body temperature regulation.

Feedback Effect of Thyroid Hormone:

• High thyroid hormone levels directly inhibit TSH secretion from the pituitary,
maintaining a stable hormone concentration.
• There might also be some indirect feedback through the hypothalamus.

Antithyroid Substances:

• These substances can block thyroid hormone production:

o Thiocyanate ions: Compete with iodide uptake by the thyroid gland.
o Propylthiouracil: Blocks the formation of thyroid hormones from iodide
and tyrosine.
o High concentration of inorganic iodides:
▪ Reduces iodide trapping and hormone formation.
▪ Paralyses the release of hormones from storage.
▪ Shrinks the thyroid gland and reduces blood supply (opposite of
other antithyroid agents).

These antithyroid drugs can lead to goiter formation (enlarged thyroid gland) due to
increased TSH stimulation without sufficient hormone production.

Diseases of the Thyroid - Hyperthyroidism:

This passage discusses the effects of thyroid hormone on sexual function, regulation
of thyroid hormone secretion, and antithyroid substances that suppress thyroid
secretion. Here's a detailed summary:

**Effects on Sexual Function:**

- Thyroid hormone plays a role in normal sexual function, and deviations from normal
thyroid secretion levels can affect libido and menstrual cycles.

- In men, lack of thyroid hormone can cause loss of libido, while an excess may
sometimes cause impotence.

- In women, lack of thyroid hormone can lead to excessive and frequent menstrual
bleeding, irregular periods, or even amenorrhea (absence of menstrual bleeding).

- Hyperthyroidism in women can cause oligomenorrhea (greatly reduced bleeding) or

amenorrhea.

**Regulation of Thyroid Hormone Secretion:**

- Feedback mechanisms through the hypothalamus and anterior pituitary gland
control the rate of thyroid hormone secretion to maintain normal metabolic activity.

- Thyrotropin-releasing hormone (TRH) from the hypothalamus stimulates the

anterior pituitary gland to increase its output of thyroid-stimulating hormone (TSH).

- TSH, in turn, increases secretion of thyroxine (T4) and triiodothyronine (T3) by the
thyroid gland.

- TRH secretion is influenced by various factors, including cold exposure and

emotional reactions, such as excitement and anxiety.

**Antithyroid Substances:**

- Thiocyanate ions, propylthiouracil, and high concentrations of inorganic iodides are

antithyroid substances that suppress thyroid secretion.

- Thiocyanate ions compete with iodide ions for transport into the thyroid cells,
inhibiting iodide trapping and, thus, thyroid hormone formation.

- Propylthiouracil blocks the peroxidase enzyme required for iodination of tyrosine

and the coupling of iodinated tyrosines to form thyroid hormones.

- High concentrations of iodides decrease all phases of thyroid activity, including

iodide trapping and endocytosis of colloid from the follicles, leading to immediate
shutdown of thyroid hormone secretion.

In summary, thyroid hormone plays a critical role in sexual function, and deviations
from normal levels can impact libido and menstrual cycles. Regulation of thyroid
hormone secretion involves feedback mechanisms through the hypothalamus and
anterior pituitary gland. Antithyroid substances such as thiocyanate ions,
propylthiouracil, and high concentrations of inorganic iodides can suppress thyroid
secretion by inhibiting iodide trapping, hormone formation, and endocytosis of colloid
from the follicles.

Hyperthyroidism and Hypothyroidism: Disruptions of the Thyroid System

This passage explores two conditions affecting thyroid function: hyperthyroidism

(excess hormone) and hypothyroidism (deficiency).

Hyperthyroidism (Overactive Thyroid):

• Causes:
o Graves' disease (most common): Autoimmune disease where
antibodies stimulate the thyroid gland.
o Thyroid adenoma (tumor): Secretes excessive thyroid hormone.
• Symptoms:
 o Increased excitability, heat intolerance, sweating.
o Weight loss despite normal or increased appetite.
o Diarrhea, muscle weakness, nervousness, fatigue, insomnia.
o Exophthalmos (bulging eyeballs) in some cases, potentially damaging
vision.
• Diagnosis:
o Measurement of free thyroxine (T4) and sometimes triiodothyronine
(T3) levels.
o Basal metabolic rate (BMR) is usually elevated.
o TSH levels are typically suppressed due to feedback inhibition by high
thyroid hormone.
o TSI (thyroid-stimulating immunoglobulin) levels might be high in
Graves' disease.
• Treatment:
o Surgical removal of most of the thyroid gland.
o Preoperative treatment with propylthiouracil to normalize BMR.
o Radioactive iodine ablation: destroying thyroid tissue with radioactive
iodine.

Hypothyroidism (Underactive Thyroid):

• Causes:
o Hashimoto's disease (most common): Autoimmune destruction of the
thyroid gland.
o Endemic colloid goiter: Iodine deficiency leading to goiter formation
(enlarged gland) but impaired hormone production.
o Several other types, often associated with goiter development.
• Symptoms (generally opposite of hyperthyroidism):
o Lethargy, cold intolerance, weight gain.
o Slow heart rate, constipation, dry skin, hair loss.
o Depression, memory problems.
• Development of Endemic Goiter due to Iodine Deficiency:
o Insufficient iodine intake prevents thyroid hormone production.
o No hormone to suppress TSH secretion from the pituitary.
o Pituitary releases excess TSH, stimulating thyroglobulin production by
the thyroid gland.
o Follicles enlarge with colloid but lack sufficient iodine for hormone
formation.
o The gland keeps growing due to continuous TSH stimulation, forming a
large goiter.
Hypothyroidism: Causes, Effects, and Treatment

This passage delves into hypothyroidism, a condition resulting from insufficient

thyroid hormone production.

Causes:

• Hashimoto's disease (autoimmune destruction): Most common cause.

 • Endemic colloid goiter: Iodine deficiency leading to goiter formation but
impaired hormone production.
• Idiopathic colloid goiter: Enlarged thyroid with unknown cause, may have
normal or reduced hormone secretion.
• Other causes: Radiation treatment, surgical removal of the thyroid gland.

Symptoms:

• Fatigue, excessive sleepiness.

• Muscle weakness, slowed heart rate, decreased cardiac output.
• Decreased blood volume, weight gain (sometimes), constipation.
• Mental sluggishness, impaired growth of hair and skin.
• Hoarse voice, puffy face (myxedema) in severe cases.
• Increased blood cholesterol, risk of atherosclerosis.

Myxedema:

• Severe hypothyroidism with near-total hormone deficiency.

• Caused by buildup of hyaluronic acid and chondroitin sulfate in tissues,
leading to edema.
• Edema is non-pitting due to the gel-like nature of the excess fluid.

Diagnosis:

• Low free thyroxine in blood.

• Basal metabolic rate (BMR) is significantly reduced.
• Increased TSH secretion in response to TRH stimulation (except in rare
cases).

Treatment:

• Daily oral thyroxine medication to maintain normal hormone levels.

• Early treatment is crucial to prevent permanent mental retardation in children
with cretinism (hypothyroidism during fetal development).

Cretinism:

• Results from severe hypothyroidism during fetal life, infancy, or childhood.

• Characterized by stunted growth and mental retardation.
• Early treatment can restore normal physical growth, but mental development
might be permanently affected.
Thyroid hormone plays a crucial role in various physiological processes in the body,
including the regulation of metabolism, calcium homeostasis, and sexual function.
Here's a detailed summary of the text you provided:

1. **Formation and Regulation of Thyroid Hormone**: Thyroid hormone is

synthesized and released by the thyroid gland in response to stimulation by thyroid-
stimulating hormone (TSH) from the anterior pituitary gland. The release of thyroid
hormone is tightly regulated by a feedback mechanism involving the hypothalamus,
anterior pituitary gland, and thyroid gland.

2. **Effect of Thyroid Hormone on Metabolism**: Thyroid hormone plays a key role in

regulating the body's metabolic rate. It increases the rate of oxygen consumption and
heat production in cells, leading to increased metabolism. Thyroid hormone also
influences the breakdown of glucose, fats, and proteins for energy.

3. **Effect of Thyroid Hormone on Calcium Homeostasis**: Thyroid hormone is

essential for maintaining normal calcium levels in the body. It promotes the
absorption of calcium from the intestines and bones, and it also reduces calcium
excretion by the kidneys.

4. **Effect of Thyroid Hormone on Parathyroid Hormone**: Thyroid hormone

formation increases the need for parathyroid hormone, which is involved in calcium
regulation.

5. **Effect of Thyroid Hormone on Adrenal Glucocorticoids**: Thyroid hormone

increases the rate at which adrenal glucocorticoids are inactivated by the liver,
leading to an increase in adrenocorticotropic hormone (ACTH) production by the
anterior pituitary and an increased rate of glucocorticoid secretion by the adrenal
glands.

6. **Effect of Thyroid Hormone on Sexual Function**: Normal sexual function

requires approximately normal thyroid secretion. In men, lack of thyroid hormone
may cause loss of libido, while an excess can sometimes cause impotence. In
women, lack of thyroid hormone can cause menstrual irregularities, including
excessive bleeding or irregular periods. Hyperthyroidism in women can lead to
reduced menstrual bleeding.

7. **Regulation of Thyroid Hormone Secretion**: The secretion of thyroid hormone is

regulated by a feedback mechanism involving the hypothalamus, anterior pituitary
gland, and thyroid gland. Thyrotropin-releasing hormone (TRH) from the
hypothalamus stimulates the anterior pituitary to release TSH, which in turn
stimulates the thyroid gland to produce and release thyroid hormone.
8. **Antithyroid Substances**: Certain substances, such as thiocyanate,
propylthiouracil, and high concentrations of inorganic iodides, can suppress thyroid
secretion by interfering with iodide trapping, thyroid hormone formation, or thyroid
gland activity.

9. **Diseases of the Thyroid**: Hyperthyroidism, characterized by excessive thyroid

hormone production, can result from conditions such as toxic goiter, thyroid
adenoma, or Graves' disease. Hypothyroidism, characterized by insufficient thyroid
hormone production, can result from conditions such as Hashimoto's thyroiditis,
endemic colloid goiter, or idiopathic nontoxic colloid goiter. Myxedema is a severe
form of hypothyroidism that can lead to edema and other symptoms.

10. **Treatment of Thyroid Disorders**: Treatment of hyperthyroidism may involve

surgical removal of the thyroid gland or treatment with radioactive iodine to destroy
thyroid tissue. Treatment of hypothyroidism typically involves hormone replacement
therapy with synthetic thyroid hormone.

Please let me know if you need more specific information or clarification on any of
these points.

Answers to study unit 3:

The Thyroid Gland: Structure, Function, and Regulation

1. Microscopic Structure and Function:

The thyroid gland is a butterfly-shaped organ located in the neck. It consists of

numerous follicles, the functional units. Each follicle is lined with cuboidal epithelial
cells, called thyrocytes. These cells:

• Secrete thyroglobulin: a large glycoprotein stored in the follicle lumen

(cavity).
• Express sodium-iodide symporter (NIS): pumps iodide from the
bloodstream into the follicle against a concentration gradient.
• Express thyroperoxidase (TPO): oxidizes iodide for thyroid hormone
synthesis.

2. Synthesis, Secretion, and Transport of Thyroid Hormones:

Stimulus: Thyrotropin-releasing hormone (TRH) from the hypothalamus stimulates

the release of thyroid-stimulating hormone (TSH) from the pituitary gland.
Iodide Trapping: NIS actively transports iodide from the blood into the follicular
lumen.

Iodine Formation: TPO oxidizes trapped iodide (I-) to iodine (I+).

Thyroglobulin Formation and Secretion: Thyrocytes synthesize and secrete

thyroglobulin into the colloid. Thyroglobulin contains numerous tyrosine residues, the
building blocks for thyroid hormones.

Thyroid Hormone Formation: TPO catalyzes the covalent linkage of iodine to

tyrosine residues in thyroglobulin:

• Monoidotyrosine (MIT): one iodine atom attached.

• Diiodotyrosine (DIT): two iodine atoms attached.

Thyroglobulin Breakdown and Hormone Release: Upon TSH stimulation,

thyrocytes endocytose colloid droplets containing thyroglobulin. Proteases within
lysosomes break down thyroglobulin, releasing:

• Triiodothyronine (T3): three iodine atoms attached (active form).

• Thyroxine (T4): four iodine atoms attached (inactive form converted to T3 in
tissues).

Secretion and Transport: Released T3 and T4 enter the bloodstream and bind to
thyroxine-binding globulin (TBG) for transport to target tissues.

3. Definitions:

• Thyrotropin-releasing hormone (TRH): Stimulates TSH release from the

pituitary.
• Thyroid-stimulating hormone (TSH): Stimulates thyroid hormone synthesis
and secretion.
• Sodium-iodide-symporter (NIS): Transports iodide into the thyroid gland.
• Pendrin (chloride-iodide-countertransporter): Facilitates iodide efflux from
the thyroid.
• Peroxidase: An enzyme that oxidizes iodide.
• Iodide (I-): An ion with one iodine atom.
• Iodine (I+): An element with one iodine atom.
• Thyroglobulin: A protein precursor for thyroid hormones.
• Iodination: The process of attaching iodine to tyrosine.
• Tyrosine: An amino acid used in thyroid hormone synthesis.
• Monoiodotyrosine (MIT): Tyrosine with one iodine atom.
• Diiodotyrosine (DIT): Tyrosine with two iodine atoms.
• Triiodothyronine (T3): Active thyroid hormone with three iodine atoms.
• Thyroxine (T4): Prohormone converted to T3, has four iodine atoms.
• Pinocytosis: Cellular uptake of fluids and solutes.
• Colloid droplet: A droplet of thyroglobulin stored in the follicular lumen.
• Proteases: Enzymes that break down proteins.
• Deiodinase: An enzyme that removes iodine from thyroid hormones.
• Deiodination: Removal of iodine from thyroid hormones.
 • Thyroxine-binding globulin (TBG): A protein that transports thyroid
hormones in the blood.

4. Effects of TSH on Thyroid Hormone Secretion:

Short-term effects (minutes to hours):

• Increases iodide uptake: Stimulates NIS activity.

• Increases thyroglobulin synthesis and secretion.
• Increases T3 and T4 release from pre-formed stores.

Long-term effects (days to weeks):

• Increases thyroglobulin synthesis: Stimulates thyroid cell growth and

protein synthesis.
• Increases blood flow to the thyroid gland: Enhances substrate delivery
and hormone removal.

5. Regulation of Thyroid Hormone Secretion:

1. Hypothalamus: Releases TRH in response to low T3 levels in the blood.

2. Pituitary: Releases TSH in response to TRH.
3. Thyroid: Releases T3 and T4 in response to TSH.
4. Negative feedback: T3 and T4 inhibit TRH and TSH release, maintaining
hormonal balance.
### Overview of the Thyroid Gland

The thyroid gland is a butterfly-shaped organ located in the neck, just below the
Adam's apple. It consists of two lobes connected by a thin tissue called the isthmus.
The gland is made up of numerous spherical structures called follicles, which are
lined with follicular cells. These follicular cells produce and secrete thyroid
hormones, primarily thyroxine (T4) and triiodothyronine (T3), which play essential
roles in regulating metabolism, growth, and development in the body.

### Microscopic Structure of the Thyroid Gland

- **Follicular Cells:** These cells line the follicles and are responsible for the
synthesis and secretion of thyroid hormones.

- **Colloid:** The follicles are filled with a protein-rich substance called colloid, which
contains the precursor molecule for thyroid hormones, thyroglobulin.

- **Parafollicular Cells (C Cells):** These cells are located between the follicles and
secrete calcitonin, which helps regulate calcium levels in the body.

### Functions of Different Parts of the Thyroid Gland

- **Follicular Cells:** Synthesize and secrete thyroid hormones.

- **Colloid:** Stores thyroglobulin, which is necessary for thyroid hormone synthesis.

- **Parafollicular Cells:** Secrete calcitonin, which regulates calcium levels in the

body.

### Synthesis, Secretion, and Transport of Thyroid Hormones

1. **Stimulus for Thyroid Hormone Synthesis/Secretion:** Thyrotropin-releasing

hormone (TRH) from the hypothalamus stimulates the release of thyroid-stimulating
hormone (TSH) from the anterior pituitary gland.

2. **Iodide Trapping Inside Epithelial Cells:** Iodide is actively transported into

thyroid follicular cells by the sodium-iodide symporter (NIS).

3. **Iodine Formation:** Iodide is oxidized to iodine by thyroid peroxidase (TPO) and

hydrogen peroxide (H2O2).

4. **Thyroglobulin Formation and Secretion Into Colloid:** Thyroglobulin is

synthesized in the endoplasmic reticulum of follicular cells and secreted into the
colloid.

5. **Thyroid Hormone Formation:** Iodine is added to tyrosine residues on

thyroglobulin to form monoiodotyrosine (MIT) and diiodotyrosine (DIT), which then
combine to form T3 and T4.
6. **Thyroglobulin, Iodine, and Thyroid Hormone Formation:** Thyroglobulin is taken
back into follicular cells through pinocytosis, where proteases cleave T3 and T4 from
thyroglobulin.

7. **Thyroid Hormone Storage and Secretion Into the Circulation:** T3 and T4 are
stored in the colloid until stimulated by TSH to be released into the bloodstream.

8. **Thyroid Hormone Transport and Delivery:** T3 and T4 are bound to thyroxine-

binding globulin (TBG) and transported in the blood to target tissues.

### Regulation of Thyroid Hormone Secretion

- **TRH and TSH:** TRH stimulates the release of TSH from the anterior pituitary,
which then stimulates the thyroid gland to produce and release thyroid hormones.

- **Feedback Mechanism:** High levels of thyroid hormones inhibit the release of

TRH and TSH, while low levels stimulate their release, maintaining thyroid hormone
levels within a narrow range.
### Effects of Thyroid Hormones on Cellular and Body Functioning

- **Metabolism:** Thyroid hormones increase metabolic rate, oxygen consumption,

and heat production.

- **Growth and Development:** Thyroid hormones are essential for normal growth
and development, especially in children and during pregnancy.

- **Cardiovascular Effects:** Thyroid hormones increase heart rate, cardiac output,

and blood pressure.

- **Other Effects:** Thyroid hormones play roles in regulating body temperature,

muscle function, and the nervous system.

### Hyperthyroidism and Hypothyroidism

- **Hyperthyroidism:** Excessive production of thyroid hormones, leading to

symptoms such as weight loss, increased heart rate, and heat intolerance.

- **Hypothyroidism:** Insufficient production of thyroid hormones, leading to

symptoms such as fatigue, weight gain, and cold intolerance.