Chapter 18

The Endocrine System

Endocrine system
Endo = inside crine = secrete hormon = to excite
to get ~ 1# of endocrine tissue you would need to collect ALL the endocrine tissue from ~4-5 adults

Exocrine cells secrete their product into a duct

Homeostasis
Works in conjunction w/ nervous system slower to react/effects last longer endocrine glands include:
pituitary, thyroid, parathyroid, adrenal, pineal, thymus, ORGANS pancreas, gonads, hypothalamus (neuroendocrine organ), MINOR ORGANS - sm int., stomach, kidneys, heart, adipose cells

Paracrines
locally acting chemicals that transfer information from cell to cell within single tissue
These are not considered hormones since hormones are long-distance chemical signals

Hormone-target cell specificity

A cell can only react to a H if it has a receptor on its plasma membrane or in its interior example: radio tuned to only pick up specific signals although there are many signals in the air concurrently

3 factors effecting target cell activation

1. Blood levels of the H 2. # of receptors for that H on or in target cells 3. affinity (strength) of bond b/t H & receptor
up-regulation - target cells form more receptors in response to decreased blood H levels down-regulation - prolonged exposure to high H [ ] desensitizes the target cell by losing receptors so they respond less vigorously to H stimulation

Mechanism of Hormone action

Hormones have their effect by altering cell activity, not causing the activity
alters plasma membrane permeability alters membrane potential thru open/closing ion channels (+) synthesis of proteins/enzymes w/in cell activates/deactivates enzymes induces secretory activity stimulates mitosis

Hormones
Can be divided into 3 groups:
amino acid derivatives peptide hormones lipid derivatives

Amino Acid Derivatives

Small molecules structurally related to amino acids Synthesized from the amino acids tyrosine and tryptophan

Peptide Hormones
Chains of amino acids Synthesized as prohormones:
inactive molecules converted to active hormones before or after secretion

2 Groups of Peptide Hormones

Group 1:
glycoproteins:
more than 200 amino acids long, with carbohydrate side chains:
TSH, LH, FSH

Group 2:
all hormones secreted by:
hypothalamus hypophysis heart thymus digestive tract pancreas

2 Classes of Lipid Derivatives

Eicosanoids:
derived from arachidonic acid

Steroid hormones:
derived from cholesterol

Eicosanoids
act locally so are not always thought of as Hs b/c they are not circulating in the blood examples:
leukotrienes - signaling chemicals that mediate inflammation & some allergic reactions prostaglandins - multiple functions including raising of BP, enhancement of uterine contractions, blood clotting, & inflammation

Steroid Hormones
Are lipids structurally similar to cholesterol Released by:
reproductive organs adrenal cortex (corticosteroids) kidneys (calcitriol)

Remain in circulation longer than peptide hormones Are converted to soluble form, are absorbed gradually by liver, & may be excreted in bile or urine

Hormone Concentrations in the Blood

Hormones circulate in the blood in two forms free or bound
Steroids and thyroid hormone are attached to plasma proteins and remain in circulation much longer All others are unencumbered and remain functional for less than one hour
These are either absorbed & broken down by liver or kidneys, are broken down by enzymes, or diffuse out of the bloodstream to bind on target cells

Mechanism of Hormone action

A hormone must bind to a receptor to exert its effect There are two ways in which this happens
Second messenger mechanism Using intracellular receptor

Catecholamines and Peptide Hormones

Are not lipid soluble so unable to penetrate cell membrane Bind to receptor proteins at outer surface of cell membrane (extracellular receptors) Uses intracellular intermediary (second messenger) to exert effects

cAMP as a second messenger

Intracellular Intermediaries
First messenger:
leads to second messenger may act as enzyme activator, inhibitor, or cofactor results in change in rates of metabolic reactions

Important Second Messengers

Cyclic-AMP (cAMP):
derivative of ATP

Cyclic-GMP (cGMP):
derivative of GTP

Calcium ions

Cascade Effect
When the binding of a small number of hormone molecules to membrane receptors leads to thousands of second messengers in cell Magnifies effect of hormone on target cell

G Protein
Enzyme complex coupled to membrane receptor Involved in link between first messenger and second messenger
Binds GTP

Activated when hormone binds to receptor at membrane surface Changes concentration of second messenger cyclic-AMP (cAMP) within cell
Increased cAMP level accelerates metabolic activity within cell

Lower cAMP Levels

1. Adenylate cyclase activity is inhibited 2. Levels of cAMP decline 3. cAMP breakdown accelerates & cAMP synthesis is prevented

Eicosanoids & Steroid Hormones

Are lipid soluble Diffuse across membrane to bind to receptors in cytoplasm or nucleus, activating or inactivating specific genes Alter rate of DNA transcription in nucleus:
change patterns of protein synthesis

Directly affect metabolic activity and structure of target cell

Endocrine reflex Triggers

NEGATIVE FEEDBACK SYSTEM humoral - PTH raises blood Ca, insulin, aldosterone neural - SNS to adrenals, oxytocin/ADH release from post. pituitary due to hypothalamic (+) hormonal - tropic Hs from Ant. Pit. As a result of the target gland raising H levels in blood

Hypothalamus - a neuroendocrine organ

1. Secretes regulatory hormones:
Special hormones control endocrine cells in pituitary gland

2. Contains autonomic centers:

Exert direct neural control over endocrine cells of adrenal medullae

Pituitary gland aka Hypophysis

Found in sella turcica pea sized & connected to hypothalamus via infundibulum secretes at least 9 Hs Master gland anterior (glandular) & posterior (neural)lobes

Neurohypophysis
Derived from hypothalamic tissue Connected to the hypothalamus via the infundibulum Does not synthesize its own hormones
Stores those made in the hypothalamus
Oxytocin & ADH

Adenohypophysis
Formed from epithelial tissue originating from Rathkes pouch (oral mucosa) No neural connection to hypothalamus Synthesizes its own hormones Communicates via a vascular connection
Primary capillary plexus in hypothalamus Secondary capillary plexus in ant. pituitary

Hypophyseal secretory effectors

Activity of the Adenophypophysis

The hypothalamus sends a chemical stimulus to the anterior pituitary Releasing hormones stimulate the synthesis and release of hormones Inhibiting hormones shut off the synthesis and release of hormones

Adenohypophyseal Hormones
Tropic hormones
4 out of 6 are tropic (turn on/stimulatory) TSH, ACTH, FSH, LH All adenohypophyseal Hs affect their target cells via a second messenger system

Thyroid stimulating hormone

TSHthyrotropin Release triggered by thyrotropin-releasing hormone (TRH) Somatostatin is released by hypothalamus w/ increasing TSH levels to block release

Adrenocorticotropic hormone
ACTHcorticotropin Release triggered by corticotropin-releasing hormone (CRH) (+) adrenal cortex to release corticosteroid Hs; specifically those that help the body resist stressors

Gonadotropins
Follicle stimulating hormone (FSH)
AKA follitropin Stimulates gamete production (sperm & egg)

Luteinizing hormone (LH)

AKA lutotropin Promotes production of gonadal hormones Stimulates maturation of the ovarian follicle and then triggers ovulation Stimulates interstitial cells of testes to produce testosteroneAKA interstitial cell stimulating hormone (ICSH)

Virtually non-existant in prepubescents Release regulated by gonadotropin-releasing hormone (GnRH) & suppressed by rising levels of gonadal Hs

Prolactin (PRL)
AKA mammotropin Some people consider it a gonadotropin but structurally similar to GH Well documented to (+) milk production in breasts May enhance testosterone production in males Release controlled by both prolactin-releasing hormone (PRH)thought to be serotonin & prolactin-inhibiting hormone (PIH)thought to be dopamine
PIH dominates in males In women PRL levels rise & fall w/ estrogen levels (low estrogen(+) PIH release/high estrogen(+) PRHwhen just prior to menstruation accounts for breast swelling & tenderness

Growth hormone (GH)

AKA Somatotropin (STH) Major targets are bone & sk mm cells
(+) most body cells to grow & divide Encourages protein synthesis & use of fat for fuel

Secretion is regulated by 2 hypothalamic Hs

Growth hormone-releasing hormone (GHRH) Growth hormone-inhibiting hormone (GHIH)
Aka somatostatin (also (-) other ant.pit. Hs, GI, & pancreatic secretionsboth endo & exocrine)

Melanocyte Stimulating Hormone

Also called melanotropin (MSH) Stimulates melanocytes to produce melanin Inhibited by dopamine Secreted during:
fetal development early childhood pregnancy certain diseases

Summary: The Hormones of the Pituitary Gland

Table 182

Neurohypophyseal Hormones
ADH & Oxytocin Both composed of 9 Aas & are almost identical
Differ in only 2 of 9 AAs

Antidiuretic hormone (ADH)

Inhibits or prevents urine formation Hypothalamus has osmoreceptors to monitor blood solute [ ]
If too [ ] ADH is released which causes kidneys to resorb more water Other (+) include: pain, hypotension, nicotine, morphine (-) by alcohol & caffeine

At high blood [ ] ADH has a vasoconstrictive effectconditions such as severe blood loss cause ADH release which causes a rise in BP
Aka Vasopressin

Diabetes insipidus
Deficiency of ADH Leads to huge amounts of urine production Insipidus = tastelessno glucosuria OK if thirst centers intact
Dangerous in unconscious patients & w/head injury Head trauma victims must be carefully monitored

Oxytocin
A strong stimulant of uterine contraction
Amounts higher during childbirth & w/nursing Stretching of the uterus & cervix sends afferent signals to the hypothalamusrelease of more oxytocin

Triggers milk letdown or ejection in lactating breasts ) from PRL

Both are positive feedback mechanisms

Oxytocin, cont.
Natural & synthetic drugs (pitocin) are used to induce labor & speed it up Sometimes used to stop postpartum bleeding (compressing of ruptures blood vessels) May play role in sexual satisfaction & orgasm in males & non-lacting females
May promote nurturing/affectionate behavior in non-sexual relationshipscuddling hormone

Thyroid gland
Butterfly shaped w/2 lobes connected by an isthmus Made up of 2 types of cells Follicle cells (simple cuboidal or squamous epithelium) make up the follicle & produce a glycoprotein called thyroglobulin The lumen of the follicle contains thyroglobulin w/ attached Iodine molecules Thyroid hormone (TH) is produced from the iodinated thyroglobulin Parafollicular cells are interspersed b/t follicular epithelium & the CT separating the follicles Calcitonin is produced here

Thyroid Gland

Figure 1810a, b

Thyroid Hormone (TH)

The bodys major metabolic hormone Actually 2 different Hs:
T4 or thyroxin (major H secreted by follicle cells) T3 or triiodothyronine (most formed at target tissues by converting T4 to T3)

Affects virtually every body cell except adult brain, spleen, testes, uterus, & the thyroid gland itself

TH, cont.
Stimulates enzymes concerned w/glucose oxidationincreases BMR Increases body heat production (calorigenic effect) Increases # of adrenergic receptors in BVs so it is important in maintaining BP Regulator of tissue growth & development (esp skeletal, nervous, & reproductive system)also affects CV system, mm system, GI system, & hydration of skin

Synthesis of Thyroid Hormone

TH regulation
Falling thyroxin blood levels trigger release of TSHthyroxin TSH levels are usually lower during the day, peak just b/f sleep, & remain high during the night Conditions that increase the bodys energy requirements (pregnancy, prolonged cold) cause hypothalamus to release thyrotropin-releasing hormone (TRH)TSH release from ant. pit.
TRH overcomes the (-) feedback controls

Somatostatin, rising levels of glucocorticoids & sex Hs (estrogens & testosterone), & excessively high blood iodide [ ] all (-) TSH release

Thyroid disorders
Hypothyroid
Myxedema low BMR, feel cold, constipation, thick/dry skin, puffy eyes, edema, lethargy, mental sluggishness
if it is a result of iodine insufficiency the thyroid gland enlarges to form a colloidal goiter (follicle cells produce colloid & store it but cannot iodinate itTSH secretion increasesmore colloid produced but no THafter a while thyroid cells burn out & gland atrophies)

Cretinism severe hypothyroid in infants; usually mentally retarded, short, disproportioned body, thick tongue; may be a genetic defect in thyroid or inadequate maternal dietary iodine intake

Hyperthyroid
Graves disease believed to be autoimmune; increased BMR, sweating, rapid heart rate, nervousness, weight loss, exophthalmos (from edematous accumulation b/h eyes)

Exophthalmos

Colloidal goiter

Calcitonin
Produced by the parafollicular (C-clear) cells Antagonist to PTH by lowering blood calcium levels
(+) Ca uptake & incorporation into bone matrix (-) osteoclast activitybone resorption

Excessive blood Ca levels (~20% above normal) (+) calcitonin release Declining blood Ca levels (-) release Seems more important in childhood w/rapidly growing bones & rapidly changing blood Ca levels In adults it is a weak hypocalcemic agent

Parathyroid glands
Usually 4 BB sized glands found on the posterior aspect of the thyroid gland Secretion of PTH is by chief cells As many as 8 glands have already been found and some have even been found in other areas of the neck & thorax

Parathyroid hormone (PTH)

AKA parathormone Single most important H controlling Ca balance in the blood (+) from falling blood Ca levels (-) from hypercalcemia PTH release (+) 3 target organs

PTH, cont.
PTH release (+)
Osteoclasts to digest bony matrix & release Ca & phosphates to the blood Kidneys to enhance reabsorption of Ca (& excretion of phosphates) Intestine increases absorption of Ca by intestinal mucosa cells PTH causes conversion of vitamin D from the inactive form absorbed in the skin into its active form, calcitriol
Vit D is needed to absorb Ca from ingested food

Adrenal glands
AKA suprarenal glands Dual glands
Adrenal medulla nervous tissue (SNS) Adrenal cortex glandular tissue derived from embryonic mesoderm; majority of gland

All adrenal hormones help us cope with extreme (stressful) situations

Adrenal cortex
Produce over 2 dozen steroid Hs called corticosteroids 3 distinct layers or zones of cells
Zona glomerulosa produce mineralocorticoids
Balance of water & minerals in body

Zona fasciculata produce glucocorticoids

Metabolism of body cells, gluconeogenesis, anti-inflammatory

Zona reticularis produce gonadocorticoids

Insignificant in adults, female libido?

All corticosteroids are produced by some degree in all 3 layers

Mineralocorticoids
Aldosterone is the most potent (95% of total); (+) distal tubules in kidneys to reabsorb Na ions from the forming urine & return them to bloodstream (same result of Na reabsorption from perspiration, saliva, & gastric juices)
Rememberwhere Na goes, water will follow (+) of aldosterone secretion: hyperkalemia, hyponatremia, decreasing blood volume & decreasing BP (-) of secretion is due to the reverse factors ACTH has little to no effect on aldosterone release

Glucocorticoids
Cortisol is the most important; help keep blood glucose levels constant w/sporadic meal patterns, very active responding to stress, antiinflammatory
Secretion promoted by ACTH Any stress will cause override of (-) feedback that normally would reduce cortisol levels Cortisol also enhances epinephrines vasoconstrictive effects to increase BPensuring circulatory efficiency to help distribute nutrients

Glucocorticoids, cont.
Excessive levels of cortisone:
Depress cartilage & bone formation (-) inflammation by preventing vasodilation Depresses the immune system Promotes changes in cardiovascular, neural, & GI function

Frequently are the drug of choice for chronic inflammatory diseases

Cortisone diseases
Hypersecretion
Cushings disease (syndrome) most often results from overmedication; also adrenal cortex tumors or tumors of pituitary causing release of ACTH
Hyperglycemia, loss of mm/bone protein, salt/water retentionmoon face, buffalo hump from fat redistribution, easy bruising, poor wound healingtx w/ discontinuing drugs or removal of tumor

Hyposecretion
Addisons disease usually deficits of both glucocorticoids (cortisone) & mineralocorticoids (aldosterone)
Weight loss, drop of plasma glucose & Na levels, rise in K levelsdehydration, hypotensiontx w/corticosteroid replacement

Cushing Syndrome

Gonadocorticoids
AKA sex hormones Most are androgens; testosterone is most important Minimal amounts of estrogen production Not much function in the adultadrenal androgens seem to be related to the female sex drive (libido)
May convert to estrogens after menopause when ovarian estrogens are no longer produced

Adrenal medulla
Chromaffin cells are modified ganglionic sympathetic neurons that secrete the catecholamines
Epinephrine Norepinephrine

Catecholamines
SNS fibers w/ fight or flight
Blood sugar levels rise, vasoconstriction, tachycardia, diversion of blood from nonessential organs to brain, heart, & skeletal mm

Catecholamines released after SNS (+) prolong response; response is brief in relation to effects of adrenocortical Hs 80% of Hs released are epi, 20% are norepi
Epi is more potent for (+) heart & metabolic activities Norepi is more potent for (+)vasoconstriction & BP Epi is often used clinically as a heart stimulant and a bronchioldilator during asthma attacks

Pineal Gland
Small gland hanging from the roof of the third ventricle of the brain Secretory product is melatonin Melatonin is involved with:
Inhibits reproductive functions Protects against free radical formation Day/night cycles & physiological processes that show rhythmic variations (body temperature, sleep, appetite)

Pancreas
A triangular gland, which has both exocrine and endocrine cells, located behind the stomach Acinar cells produce an enzyme-rich juice used for digestion (exocrine product) Pancreatic islets (islets of Langerhans) produce hormones (endocrine products) The islets contain four cell types:
Alpha (E) cells that produce glucagon Beta (F) cells that produce insulin Delta ( ) cells that produce somatostatin F-cells secrete pancreatic polypeptide (PP) (-) g. bladder

Insulin
Produced by beta cells (islets of Langerhans) Major effect is lowering of blood sugar; also affects protein & fat metabolism Insulin enhances membrane transport of glucose into body cells like mm & fat cellsnot liver, brain, & kidney tissue--these have easy access to glucose regardless of insulin levels Main (+) is hyperglycemia
Any hyperglycemic H can also (+) release: glucagon, epi, GH, thyroxine, or glucocorticoidsall are called into action as blood glucose levels drop

Glucagon
Produced by alpha cells (islets of Langerhans) Major target is the liver
Promotes glycogenolysis; gluconeogenesis from lactic acid, fats & AAs

1 molecule of glucagon can cause the release 100 million molecules of glucose in to the blood Secretion (+) by falling blood sugar levels Secretion (-) by rise in blood sugar & somatostatin

Diabetes mellitus (DM)

Hyposecretion or inactivity of insulin 3 cardinal signs Polyuria decreased blood volume & dehydration Polydipsia thirst centers (+) from dehydration Polyphagia b/c present glucose cannot be used & body starts breaking down fat & protein stores for energy metabolism

Gonads: Male
Testes located in an extra-abdominal sac (scrotum) produce testosterone & Inhibin (sperm maturation) Testosterone:
Initiates maturation of male reproductive organs Causes appearance of secondary sexual characteristics and sex drive Is necessary for sperm production Maintains sex organs in their functional state

Gonads: Female
Paired ovaries in the abdominopelvic cavity produce estrogens and progesterone They are responsible for:
Maturation of the reproductive organs Appearance of secondary sexual characteristics Breast development and cyclic changes in the uterine mucosa

Thymus
Lobulated gland located deep to the sternum in the thorax Major hormonal product is thymosin This hormone is essential for the development of the T lymphocytes (T cells) of the immune system

Other Hormone-Producing Structures

Heart produces atrial natriuretic peptide (ANP), which reduces blood pressure, blood volume, and blood sodium concentration Gastrointestinal tract enteroendocrine cells release local-acting digestive hormones Placenta releases hormones that influence the course of pregnancy Kidneys secrete erythropoietin, which signals the production of red blood cells; & renin which is a powerful vasoconstrictor Skin produces cholecalciferol, the precursor of vitamin D Adipose tissue releases leptin, which is involved in the sensation of satiety, and stimulates increased energy expenditure; resistin reduces insulin sensitivity

Interaction of Hormones at Target Cells

Four types of hormone interaction
Permissiveness one hormone cannot exert its effects without another hormone being present Synergism more than one hormone produces the same effects on a target cell Antagonism one or more hormones opposes the action of another hormone Integration hormones produce different & complementary effects

General Adaptation Syndrome (GAS)

AKA stress response How bodies respond to stress-causing factors Divided into 3 phases: 1.alarm phase 2.resistance phase 3.exhaustion phase
Figure 1818

Alarm Phase
Is an immediate response to stress directed by ANS Energy reserves mobilized (glucose) Fight or flight responses Dominant hormone is epinephrine

7 Characteristics of Alarm Phase

1. 2. 3. 4. Increased mental alertness Increased energy consumption Mobilization of energy reserves (glycogen and lipids) Circulation changes: increased blood flow to skeletal muscles decreased blood flow to skin, kidneys, and digestive organs 5. Drastic reduction in digestion and urine production 6. Increased sweat gland secretion 7. Increases in blood pressure, heart rate, and respiratory rate

Resistance Phase
Entered if stress lasts longer than few hours Dominant hormones are glucocorticoids Energy demands remain high Glycogen reserves nearly exhausted after several hours of stress

Effects of Resistance Phase

1. Mobilize remaining lipid and protein reserves 2. Conserve glucose for neural tissues 3. Elevate and stabilize blood glucose concentrations + + 4. Conserve salts, water, and loss of K , H

Exhaustion Phase
Begins when homeostatic regulation breaks down Failure of 1 or more organ systems will prove fatal Mineral imbalance

Interactions between Endocrine and Other Systems

Figure 1819