7.

1 Principles of Endocrinology
• Endocrinology - the study of the
evolution and physiological function of
hormones.
• The endocrine system regulates and
coordinates distant organs through
the secretion of hormones.
• Hormones are signal molecules
delivered by circulatory fluids and act
on target cells.
• The endocrine system controls
activities that require duration rather
than speed.
 Graves disease

Acromegaly

Rickets
Goiter
Cretinism Gigantism

When the endocrine homeostasis fails…

TABLE 1-5 2
Figure 1-1 Chemical bioregulation. The endocrine system, nervous system, and immune system each
secretes its own bioregulators: hormones, neurocrines, and cytocrines, respectively. However, all of these
systems influence each other, and from a homeostatic viewpoint we can assume they function as one great
bioregulatory system.

Copyright © 2013 Elsevier Inc. All rights reserved. 3

 ENDOCRINOLOGY CRASH COURSE

https://www.youtube.com/watch?v=eWHH9je
2zG4&t=102s

4
WHERE IS YOUR LIVER?

5
ENDOCRINE GLANDS

6
The mammalian endocrine system
7.1 Principles of Endocrinology cont’d

• Chemical classification of
hormones:
1) Peptide and protein hormones
2) Amines
1) catecholamines
2) thyroid hormones
3) Steroids
• Differ in permeance and localization of
receptors
7.1 Principles of Endocrinology cont’d

• Hormone synthesis and

secretion:
• Peptide hormones
• Steroid hormones
• Cholesterol - synthesized or
obtained from diet
• Chemically modified – enzyme-
catalyzed reactions
• Once synthesized, immediately
diffuse from cell
Steroidogenic pathways for the major steroid hormones
Mechanism
of action of
lipophilic
hormones
 -

Negative feedback

Figure 1-4 Functional conceptualization of the endocrine system. Input from other endogenous or
exogenous factors can affect every level of regulation. The endocrine (only) glands typically respond to levels of
chemicals in the blood, and, although innervated, their secretion is not directly controlled by the nervous system.
Nonapeptide targets include the kidney and mammary gland as well as reproductive and vascular smooth
muscle. Endocrine glands controlled by tropic hormones from the pituitary include the gonads, thyroid, adrenal
cortex, and liver. Endocrine-only glands include the parathyroids, kidneys, heart, adipose tissue, and others.

Copyright © 2013 Elsevier Inc. All rights reserved. 13

7.1 Principles of Endocrinology cont’d
• Regulation of plasma
concentration of hormones:
• Negative feedback control
• When plasma hormone levels
fall, hormone secretion is
stimulated.
• Neuroendocrine reflexes
• Produce a sudden increase in
hormone secretion in response
to a specific stimulus
7.1 Principles of Endocrinology cont’d

• Regulation of plasma concentration

of hormones:
• Biological rhythms
• Secretion of most hormones
fluctuates rhythmically as a function
of time (biological clocks).
• Readjustment of set point by CNS
• Example: Cortisol secretion rises
at night to peak in early morning
(diurnal rhythm).
Diurnal rhythm of cortisol secretion
7.3 Vertebrate Endocrinology:
Central Endocrine Glands
• Pineal gland
• Secretes melatonin
• Maintains circadian rhythms
• Melatonin secretion increases up to 10-fold in
darkness.
• Seasonal changes in melatonin secretion
patterns trigger reproduction.
• In mammals melatonin output is controlled
by the suprachiasmatic nucleus (SCN) of
the hypothalamus.
• SCN receives light information from the eyes.
7.3 Vertebrate Endocrinology:
Central Endocrine Glands cont’d
• Pituitary gland (hypophysis)
• Located at the base of the brain, connected to the
hypothalamus by the infundibulum
• Posterior pituitary (neurohypophysis)
• Nervous tissue
• Anterior pituitary (adenohypophysis)
• Glandular epithelial tissue
• Intermediate lobe (pars intermedia)
• Absent in birds and cetaceans
• Rudimentary in humans after birth
• Size of intermediate lobe correlates with ability of
animal to adapt to coloration of its environment
Anatomy of the pituitary gland
7.3 Vertebrate Endocrinology:
Central Endocrine Glands cont’d
• Intermediate lobe
• Secretes melanocyte-stimulating
hormone (MSH)
• α-MSH controls skin coloration via productin
and dispersion of melanosomes.
• In lower vertebrates, α-MSH is opposed by
melanin-concentrating hormone (MCH).
• Melanocortin-1 receptor (MC1R) = MSH
receptor.
• Excessive MSH secretion darkens human skin
• MSH reduces appetite and suppresses immune
system
7.3 Vertebrate Endocrinology:
Central Endocrine Glands cont’d
• Posterior pituitary
• Connects to the hypothalamus by a neural
pathway
• Neurosecretory neurons have cell bodies in
supraoptic and paraventricular nuclei of
hypothalamus.
• Axons terminate on capillaries in posterior
pituitary.
• Secretes vasopressin and oxytocin
• Evolutionary precursor, arginine vasotocin,
is found in many vertebrates.
7.3 Vertebrate Endocrinology:
Central Endocrine Glands cont’d
• Posterior pituitary hormones:
• Oxytocin
• Social bonding
• Contraction of uterine smooth
muscle
• Ejection of milk from mammary
glands
Relationship of
the hypothalamus
and posterior
pituitary
7.3 Vertebrate Endocrinology:
Central Endocrine Glands cont’d
• Anterior pituitary hormones
1) Growth hormone (GH, somatotropin)
• Stimulates growth and affects metabolism
2) Thyroid-stimulating hormone (TSH, thyrotropin)
• Stimulates thyroid hormone secretion by thyroid gland
3) Adrenocorticotropic hormone (ACTH, corticotropin)
• Stimulates cortisol secretion by the adrenal cortex
4) Follicle-stimulating hormone (FSH)
• Regulates gamete production
5) Luteinizing hormone (LH)
• Regulates sex hormone secretion
• Ovulation and formation of corpus luteum in females
6) Prolactin (PRL)
• Stimulates milk production by mammary glands
• Wide range of additional actions
7.3 Vertebrate Endocrinology:
Central Endocrine Glands cont’d
• Hypothalamic releasing and
inhibiting hormones:
1) Thyrotropin-releasing hormone
(TRH)
2) Corticotropin-releasing hormone
(CRH)
3) Gonadotropin-releasing hormone
(GnRH) stimulates release of FSH
and LH
7.3 Vertebrate Endocrinology:
Central Endocrine Glands cont’d
• Hypothalamic releasing and
inhibiting hormones cont’d:
4) Growth hormone-releasing
hormone (GHRH)
5) Growth hormone-inhibiting
hormone (GHIH, somatostatin)
6) Prolactin-releasing hormone
(PRH)
7) Prolactin-inhibiting hormone (PIH)
Hierarchic
chain of
command in
endocrine
control
7.3 Vertebrate Endocrinology:
Central Endocrine Glands cont’d
• Hypothalamic releasing and
inhibiting hormones:
• Releasing and inhibiting hormones reach
the anterior pituitary through the
hypothalamic-hypophyseal portal system
• Regulation of hypophysiotropic hormone
secretion
• Neural input (e.g. CRH secretion in response to
stress)
• Negative-feedback effects of anterior pituitary or
target gland hormones (e.g. cortisol levels above a
set point inhibit CRH and ACTH secretion)
Hierarchic chain of command in endocrine control.
7.4 Endocrine Control of Growth
and Development in Vertebrates
• Growth depends on:
• Adequate diet
• Malnourished animals do not reach full growth
potential.
• Seasonally shortened day length reduces
growth by reducing food intake.
• Freedom from chronic disease and
stressful environmental conditions
• Glucocorticoids secreted during stress inhibit
growth.
• Growth-influencing hormones
• Placental hormones promote fetal growth.
• Growth hormone and other hormones promote
growth after birth.
7.4 Endocrine Control of Growth and
Development in Vertebrates cont’d
• Direct effects of growth hormone
(GH)
1) Metabolic effects
• Target organs are adipose tissue,
skeletal muscles and liver.
• Mobilizes fat stores as a major energy
source
• Conserves glucose for use by the brain
• Decreases glucose uptake by muscles and
increases glucose output by the liver
2) Enhances immune system
7.4 Endocrine Control of Growth and
Development in Vertebrates cont’d

•Growth hormone’s
(GH) growth-
promoting actions
are mediated by
insulin-like growth
factors (IGFs)
7.4 Endocrine Control of Growth and
Development in Vertebrates cont’d
• GH/IGF’s growth promoting
effects:
• Growth of soft tissues
• Increases number of cells
(hyperplasia)
• Increases size of cells
(hypertrophy)
• Promotes uptake of amino acids
into cells
• Stimulates protein synthesis and
7.4 Endocrine Control of Growth and
Development in Vertebrates cont’d
• GH/IGF’s growth promoting
effects:
• Growth of bone
• Promotes increases in bone
thickness and length
• Thickness depends on addition of
new bone by osteoblasts
• Length depends on proliferation of
cartilage cells (chondrocytes) in
epiphyseal plates and invasion by
osteoblasts
Anatomy of long bones
Two sections of the same epiphyseal plate at
different times, depicting the lengthening of long
bones.
7.4 Endocrine Control of Growth and
Development in Vertebrates cont’d
• Regulation of growth hormone
secretion
• Negative feedback loop involving
hypothalamus-pituitary-liver axis
• IGF-I inhibits secretion of GH by
somatotropes in anterior pituitary.
• IGF-I inhibits GHRH-secreting cells
and stimulates somatostatin-
secreting cells in hypothalamus.
7.4 Endocrine Control of Growth and
Development in Vertebrates cont’d

• Regulation of growth hormone

secretion
• Other stimuli to GH secretion
• Onset of sleep
• Exercise, stress, and hypoglycemia
• High protein meal
• Ghrelin – appetite-stimulating
hormone secreted by stomach
Control
of growth
hormone
secretion
7.4 Endocrine Control of Growth and
Development in Vertebrates cont’d
• Growth hormone administration
• Increases bone growth
• Treatment of dwarfism in humans
• Increases muscle mass
• Abuse by athletes
• Improved meat production in swine
• Increases milk production in dairy
cattle
 7.5 Thyroid Gland
• Thyroid gland
• located in the throat
below the larynx
• Composed of follicular
cells arranged in fluid-
filled spheres (thyroid
follicles)
• Colloid serves as an
extracellular storage site
Thyroid
for thyroid hormones in
gland the form of thyroglobulin,
a large glycoprotein.
The thyroid gland consists primarily of colloid-filled
spheres enclosed by a single layer of follicular cells.
7.5 Thyroid Gland cont’d
• Thyroid hormone synthesis
1. Thyroglobulin (Tg) is synthesized by thyroid
follicular cells (incorporating tyrosine) and
secreted into colloid by exocytosis.
2. Thyroid follicular cells efficiently capture iodide
(I-), obtained from the diet, using a
sodium/iodide symporter.
3. Iodide is activated and attached to tyrosine
molecules on Tg in colloid.
a) Monoiodotyrosine (MIT) has one iodine.
b) Diiodotyrosine (DIT) has two iodines.
4. Iodinated tyrosines couple to form
tetraiodothyronine (T4, thyroxine) and
triiodothyronine (T3).
Synthesis, storage, and secretion of thyroid hormone
7.5 Thyroid Gland cont’d
• Secretion of thyroid hormones
1. Follicular cells take up a piece of
colloid (containing iodinated Tg) by
endocytosis.
2. Lysosomal enzymes split off T4, T3,
MIT and DIT in the process of
breaking down Tg.
3. T4 and T3 (biologically active thyroid
hormones) diffuse across follicular
cell membrane into blood, while MIT
and DIT are recycled to iodide and
tyrosine.
Synthesis, storage, and secretion of thyroid hormone
7.5 Thyroid Gland cont’d
• Mechanism of thyroid hormone
action
• T3 is the major biologically active
form of thyroid hormone.
• T3 binds with nuclear receptors
attached to thyroid-response
elements of DNA.
• Alters transcription of specific
mRNAs and synthesis of specific
proteins.
7.5 Thyroid Gland cont’d
• Effects of thyroid hormones
• Increase basal metabolic rate (BMR);
increased mitochondrial and Na+-K+ pump
activity
• Molting in birds and mammals
• Sympathomimetic effect -- increase target
cell responsiveness to catecholamines
• Increase heart rate and force of contraction
• Essential for growth (permissive effect on
GH)
• Development of CNS
• Metamorphosis in amphibians
Thyroid hormones and amphibian metamorphosis
7.5 Thyroid Gland cont’d
• Regulation of thyroid hormone
secretion
• Negative feedback loop involving
hypothalamus-pituitary-thyroid axis
• Thyroid-stimulating hormone (TSH)
stimulates almost every step of thyroid
hormone synthesis and secretion.
• Hypothalamic thyrotropin-releasing
hormone (TRH) stimulates TSH secretion
by thyrotropes in anterior pituitary.
• Elevated T3 and T4 levels inhibit TSH
secretion.
7.5 Thyroid Gland cont’d
• Other factors
affecting thyroid
hormone
secretion
• Stress inhibits
TSH secretion.
• Cold stimulates
TSH secretion
(infants).