Endocrine Physiology
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Regulation of homeostasis
1. The nervous system: Regulates homeostasis by releasing
chemical messengers called neurotransmitters
2. The endocrine system:
Regulates homeostasis by releasing chemical messengers
called hormones
Difference b/n hormones and NTs
• Speed of action
• Duration of action
• Distribution
Common aspects:
– small quantities
– regulate other cells & tissues
– act through receptors
– functional overlap between some hormones &
neurotransmitters
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Nervous system
•The endocrine system
broadcasts its hormonal
messages to essentially all
cells by secretion into blood
H
and extra cellular fluid. Like
Nerve Impulse a radio broadcast, it requires
a receiver to get the message
- in the case of endocrine
messages, cells must bear a
R receptor for the hormone
being broadcast in order to
NTs respond.
R
Effector cell
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A cell is a target because is has a specific
receptor for the hormone
Most hormones circulate in blood, coming into contact
with essentially all cells. However, a given hormone
usually affects only a limited number of cells,
which are called target cells. A target cell responds
to a hormone because it bears receptors for the
hormone.
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Agonist vs. Antagonist
• Agonists are molecules that bind the
receptor and induce all the post-receptor
events that lead to a biologic effect. In other
words, they act like the "normal" hormone,
although perhaps more or less potently
• Antagonists are molecules that bind the
receptor and block binding of the agonist,
but fail to trigger intracellular signaling
events
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Intercellular signaling
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Principal functions hormones
1. Regulation of reproduction: gametogenesis,
sexual desire, coitus, fertilization.
2. Regulation of body growth and development.
3. Production, utilization and storage of energy
4. Homeostasis: maintenance of the internal
environment in the body (maintaining the
optimum biochemical environment).
-Water-electrolyte balance (stability of
body fluid composition eg. ADH,
Aldosterone)
-Regulation of acid-base balance
-Regulation of ABP, HR
-Control of BT, emotion
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-Change in mass of bone, muscle and fat
Chemical nature of hormones
1. Amines: derived from tyrosine
• Hydroxylation - catecholamines
• Iodination - thyroid hormones
2. Polypeptides/Peptides or proteins
– Polypeptides:
• Chains of < 100 amino acids in length. eg ADH.
– Protein hormones:
• Polypeptide chains with > 100 amino acids.
– Growth hormone.
3. Steroids (derived from cholesterol)
• Adrenocorticoids
• Sex hormones
• Active metabolites of vitamin D3
4. Eicosanoids (derived from fatty acids)
- Prostaglandins, Leukotrienes and
Thromboxanes 8
Amine Hormones: Structure
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Steroid Hormones: Structure
Figure 7-6: Steroid hormones are derived from cholesterol 10
Steroid hormones
All steroid hormones are derived from
cholesterol and differ only in the ring
structure and side chains attached to it.
All steroid hormones are lipid soluble
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Fatty acid derivatives - Eicosanoids
Fatty Acid Derivatives - Eicosanoids
• Eicosanoids are a large group of molecules
derived from polyunsaturated fatty acids.
• The principal groups of hormones of this class are
prostaglandins, prostacyclins, leukotrienes and
thromboxanes.
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Prostaglandins (continued)
Phospholipase A
Classes of hormones
The hormones fall into two general classes
based on their solubility in water.
The water soluble (Hydrophilic hormones)
hormones are the catecholamines (epinephrine
and norepinephrine) and peptide/protein
hormones.
The lipid soluble (Lipophilic hormones)
hormones include thyroid hormone, steroid
hormones and Vitamin D3
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Types of receptors
1. Receptors for the water soluble hormones are
found on the surface of the target cell, on the
plasma membrane.
These types of receptors are coupled to various
second messenger systems which mediate the
action of the hormone in the target cell.
2. Receptors for the lipid soluble hormones reside in
the nucleus (and sometimes the cytoplasm) of the
target cell.
Because these hormones can diffuse through
the lipid bilayer of the plasma membrane, their
receptors are located on the interior of the
target cell
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Hormone: synthesis, storage, release and transport
• Site of synthesis:
Protein/peptide hormones: in the rER
Steroid hormones: in the sER
• Storage:
Protein/peptide hormones: preprohormones in vesicles
Steroid hormones: Cholesterol
• Release: Exocytosis
• Transport: hormones are transported in blood in two forms:
1. In the free form
2. In combination with plasma proteins (albumin & globulin).
It has 2 advantages
a. Prolong the biological half life of hormones
b. Serve as a reservoir of hormones
• Metabolism: metabolized in the liver or by target cells
• Excretion: urine, feces, sweat
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Protein Hormones: Synthesis and Release
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Mechanism of action of hormone action
Hormones perform their action via three
mechanisms.
• Direct membrane effect
• Via activation of the second messengers
• Direct/indirect activation of the gene
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Hormone Receptors location
• Cytosolic or Nuclear
– Lipophilic ligand
enters cell
– Often activates gene
– Slower response
• Cell membrane
– Lipophobic ligand
can't enter cell
– Outer surface
receptor Hydrophilic
– Fast response
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Direct membrane effect of hormones
Hormone
H
N
Receptor
Cell membrane
Hormone-receptor interaction alters
membrane permeability by either
•Opening or closing of pores (channels)
•Conformational change of carriers,
•Activation/inactivation of pump mechanisms 20
Second messengers involved in cell signalling
• Hormones that cannot pass through plasma membrane use 2nd
messengers.
– Catecholamine, polypeptide, and glycoprotein hormones
bind to receptor proteins on the target plasma membrane.
• Actions are mediated by 2nd messengers (signal-transduction
mechanisms).
• Examples
cAMP
cGMP
G-Proteins
Phospholipase-C/IP3
Ca/calmodulin
tyr kinases
MAP kinases
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Protein and Polypeptide Hormone Receptors
• Binds to surface
receptor
• Transduction
• System activation
– Open ion channel
– Enzyme activation
• Second
messenger
systems
• Protein synthesis
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Adenylate Cyclase-cAMP
• Polypeptide or glycoprotein hormone binds
to receptor protein causing dissociation of a
subunit of G-protein.
• G-protein subunit binds to and activates
adenylate cyclase.
• ATP cAMP + PPi
• cAMP attaches to inhibitory subunit of
protein kinase.
• Inhibitory subunit dissociates and activates
protein kinase.
Adenylate Cyclase-cAMP (continued)
• Phosphorylates
enzymes within the
cell to produce
hormone’s effects.
• Modulates activity
of enzymes present
in the cell.
• Alters metabolism
of the cell.
• cAMP inactivated
by
phosphodiesterase.
– Hydrolyzes
cAMP to
inactive
fragments.
Phospholipase-C-Ca2+
• Binding of AD/NA to -
adrenergic receptor in
plasma membrane activates
a G-protein intermediate,
phospholipase C.
– Phospholipase C splits
phospholipid (phospho
inositol diphosphate,
PIP2) into IP3 and DAG.
• Both derivatives serve
as 2nd messengers.
• IP3 diffuses through
cytoplasm to ER.
– Binding of IP3 to receptor
protein in ER causes Ca2+
channels to open.
Second messenger, cAMP
Hormones are first messengers
cAMP is the second messenger
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Second messenger cGMP
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Second messenger G
H proteins
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Tyrosine Kinase
• Insulin receptor consists of 2
units that dimerize when they
bind with insulin.
– Insulin binds to ligand–binding
site on plasma membrane,
activating enzymatic site in the
cytoplasm.
• Autophosphorylation occurs,
increasing tyrosine kinase
activity.
• Activates signaling molecules.
– Stimulate glycogen, fat and
protein synthesis.
– Stimulate insertion of GLUT-4
carrier proteins.
Activation of the gene: Steroid
Hormones:
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Regulation of hormonal secretion
Hormonal secretion is regulated by at least mechanisms.
1. Feedback regulatory mechanisms
Negative feedback mechanism (most hormones)
Positive feedback mechanism (LH- surge)
2. Nervous control of hormonal secretion
Secretion of OT, ADH, AD, NA
3. Circadian rhythm (periodic variations)
Cortisol, sex hormones
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Feedback control of hormone production
Feedback loops are used
extensively to regulate
secretion of hormones in the
hypothalamic-pituitary axis. An
important example of a negative
feedback loop is seen in control
of thyroid hormone secretion
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LH surge: the positive feedback mechanism
GnRH HT
Pituitary
activates
LH
Ovary
Estrogen
>200 µg/ml
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Episodic secretion of hormones
• The most prominent episodes of release occur
with a frequency of about one hour—referred to as
circhoral
• An episode of release longer than an hour, but less
than 24 hours, the rhythm is referred to as
ultradian
• If the periodicity is approximately 24 hours, the
rhythm is referred to as circadian
– usually referred to as diurnal because the increase in
secretary activity happens at a defined period of the
day.
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Circadian (chronotropic) control
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Regulation of hormone release
• Circadian rhythms and cortisol secretion
600
500
Cortisol
(nM)
400
300
200
100
0
09 21 09
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Time of day
Major endocrine glands
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Other organs having endocrine function
• The pineal gland:
Hormone: Melatonin
Function: Inhibits gonadal function and delays
the onset of puberty.
• The thymus gland:
Hormone: Thymopoietin
Function: Stimulates lymphocyte proliferation
• Endocrine function of the heart:
Hormone: ANP (atrial natriuretic peptide)
Function: Nartiuresis Renin secretion
GFR Aldosterone secretion
Vasodilator
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Other organs having endocrine function (cont´d)
• Endocrine function of the kidneys
Hormones: Renin, erythropietin
Calcitriol (1, 25 (OH)2 D3)
Function: RAS, Ang-II
Ang-II - A potent vasoconstrictor
- Aldosterone secretion
- ADH secretion
- Stimulates the thrist center
- Salt and water reabsorption
Ang-II receptors: AT1A-R: on BVs, renal tubules
AT1B-R: on adrenal cortex
AT2-R: on neurons
• Endocrine function of the liver
• Hormones: Erythropietin
Somatomedin-C
(1, 25 (OH)2 D3)
GIT hormones: Gastrin, Secretin, CCK, VIP, Sub-P ect.
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Summary of the Endocrine System
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Summary of the Endocrine System
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Summary of the Endocrine System
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