ENDOCRINE PHYSIOLOGY / Part ONE

2009-2010
drsherwanshal@gmail.com

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 Endocrine system maintains
homeostasis
The Endocrine System is the
major system that
maintains stable internal
environmet (Homeostasis).

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 SENSING AND SIGNALING
Endocrine “glands” synthesize and store hormones. These
glands have a sensing and signaling system .

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 ENDOCRINE VS. NERVOUS SYSTEM

Both are major communication systems in the

body
They Integrate stimuli and responses to changes
in external and internal environment
Both are crucial to coordinated functions of
highly differentiated cells, tissues and organs
Unlike the nervous system, the endocrine
system is anatomically discontinuous.

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 NERVOUS SYSTEM

The nervous system exerts

point-to-point control
through nerves, similar to
sending messages by
conventional telephone.
Nervous control is electrical
in nature and fast.

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 Hormones travel via the blood stream to
target cells
•The endocrine system broadcasts its
hormonal messages to essentially all
cells by secretion into blood and
extracellular fluid. Like a radio
broadcast, it requires a receiver to get
the message - in the case of endocrine
messages, cells must bear a receptor
for the hormone being broadcast in
order to respond.
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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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 PRINCIPAL FUNCTIONS OF THE
ENDOCRINE SYSTEM
1. Maintenance of the internal environment in
the body (maintaining the optimum
biochemical environment).
2. Integration and regulation of growth and
development.
3. Control, maintenance and instigation of
sexual reproduction, including
gametogenesis, coitus, fertilization, fetal
growth and development and nourishment
of the newborn.

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 Types of cell-to-cell Classic endocrine hormones
signaling travel via bloodstream to target
cells;
neurohormones are released
via synapses and travel via the
bloostream;
paracrine hormones act on
adjacent cells and
autocrine hormones are
released and act on the cell that
secreted them. Also,
intracrine hormones act
within the cell that produces
them.
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 Response vs. distance traveled
Endocrine action: the hormone is distributed in blood and
binds to distant target cells.
Paracrine action: the hormone acts locally by diffusing from
its source to target cells in the neighborhood.
Autocrine action: the hormone acts on the same cell that
produced it.

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13 ١٤٣١/٠٣/٥ 15:13
 MAJOR HORMONES AND SYSTEMS

Hypothalamus produces releasing factors that

stimulate production of anterior pituitary hormone
which act on peripheral endocrine gland to stimulate
release of third hormone
Posterior pituitary hormones are synthesized in
neuronal cell bodies in the hypothalamus and are
released via synapses in posterior pituitary.
Oxytocin and antidiuretic hormone (ADH)

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 Types of hormones

Hormones are categorized into four

structural groups, with members of
each group having many properties
in common:
Peptides and proteins
Amino acid derivatives
Steroids
Fatty acid derivatives - Eicosanoids

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 Peptide/protein hormones
Range from 3 amino acids to hundreds of
amino acids in size.
Often produced as larger molecular weight
precursors that are proteolytically cleaved to
the active form of the hormone.
Peptide/protein hormones are water soluble.
Comprise the largest number of hormones–
perhaps in thousands

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 Amine hormones

There are two groups of hormones

derived from the amino acid
tyrosine
Thyroid hormones and
Catecholamines

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 Thyroid Hormone

Thyroid hormones are basically a "double" tyrosine

with the critical incorporation of 3 or 4 iodine atoms.
Thyroid hormone is produced by the thyroid gland and
is lipid soluble
Thyroid hormones are produced by modification of a
tyrosine residue contained in thyroglobulin, post-
translationally modified to bind iodine, then
proteolytically cleaved and released as T4 and T3.
T3 and T4 then bind to thyroxin binding globulin for
transport in the blood

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 Thyroid hormones

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 Catecholamine hormones
Catecholamines are both
neurohormones and
neurotransmitters.
These include epinephrine, and
norepinephrine
 Epinephrine and norepinephrine are
produced by the adrenal medulla both
are water soluble
Secreted like peptide hormones

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 Synthesis of catecholamines

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 Amine Hormones

Two other amino acids are used

for synthesis of hormones:
Tryptophan is the precursor to
serotonin and the pineal hormone
melatonin
Glutamic acid is converted to
histamine

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 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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 Types of steroid hormones

Glucocorticoids; cortisol is the major

representative in most mammals
Mineralocorticoids; aldosterone being
most prominent
Androgens such as testosterone
Estrogens, including estradiol and estrone
Progestogens (also known a progestins)
such as progesterone

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 Steroid hormones
Are not packaged, but synthesized and
immediately released
Are all derived from the same parent
compound: Cholesterol
Enzymes which produce steroid
hormones from cholesterol are located
in mitochondria and smooth ER
Steroids are lipid soluble and thus are
freely permeable to membranes so are
not stored in cells

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 Steroid hormones
Steroid hormones are not water soluble so have
to be carried in the blood complexed to specific
binding globulins.
Corticosteroid binding globulin carries cortisol
Sex steroid binding globulin carries testosterone
and estradiol
In some cases a steroid is secreted by one cell
and is converted to the active steroid by the
target cell: an example is androgen which
secreted by the gonad and converted into
estrogen in the brain

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 Steroid hormone synthesis
All steroid hormones are derived from cholesterol.
A series of enzymatic steps in the mitochondria
and ER of steroidogenic tissues convert
cholesterol into all of the other steroid hormones
and intermediates.
The rate-limiting step in this process is the
transport of free cholesterol from the cytoplasm
into mitochondria.
This step is carried out by the Steroidogenic
Acute Regulatory Protein (StAR)
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 Steroid hormone synthesis
•The cholesterol precursor comes from
cholesterol synthesized within the cell from
acetate, from cholesterol ester stores in
intracellular lipid droplets or from uptake of
cholesterol-containing low density
lipoproteins.

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 1,25-Dihydroxy Vitamin D3

1,25-dihydroxy Vitamin D3 is
also derived from cholesterol
and is lipid soluble
Not really a “vitamin” as it can
be synthesized de novo
Acts as a true hormone

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 Fatty Acid Derivatives -
Eicosanoids
Arachadonic acid is the most
abundant precursor for these
hormones. Stores of arachadonic acid
are present in membrane lipids and
released through the action of various
lipases.
These hormones are rapidly
inactivated by being metabolized, and
are typically active for only a few
seconds.
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 Eicosanoids are a large
group of molecules
Fatty Acid
derived from Derivatives -
polyunsaturated fatty
acids.
Eicosanoids
The principal groups of
hormones of this class
are prostaglandins,
prostacyclins,
leukotrienes and
thromboxanes.

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 Regulation of hormone secretion

Sensing and signaling: a biological need is

sensed, the endocrine system sends out a
signal to a target cell whose action
addresses the biological need. Key features
of this stimulus response system are:
1. Receipt of stimulus.
2. Synthesis and secretion of hormone.
3. Delivery of hormone to target cell.
4. Evoking target cell response.
5. Degradation of hormone.

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 Mechanism Of Hormone
Action

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 Receptor Location

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 Control of Endocrine Activity
•The physiologic effects of hormones
depend largely on their concentration in
blood and extracellular fluid.
•Almost inevitably, disease results when
hormone concentrations are either too high or
too low, and precise control over circulating
concentrations of hormones is therefore
crucial.

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 Control of Endocrine Activity
The concentration of hormone as seen
by target cells is determined by three
factors:

•Rate of production
•Rate of delivery
•Rate of degradation and elimination

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 Control of Endocrine Activity

Rate of production: Synthesis and

secretion of hormones are the most highly
regulated aspect of endocrine control. Such
control is mediated by positive and negative
feedback circuits.

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 Control of Endocrine Activity
Rate of delivery: An example of this
effect is blood flow to a target organ or
group of target cells - high blood flow
delivers more hormone than low blood
flow.

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 Control of Endocrine Activity
Rate of degradation and elimination: Hormones,
like all biomolecules, have characteristic rates of
decay, and are metabolized and excreted from the
body through several routes.

Shutting off secretion of a hormone that has a very

short half-life causes circulating hormone
concentration to plummet, but if a hormone's
biological half-life is long, effective concentrations
persist for some time after secretion ceases.
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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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 Inputs to endocrine cells

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 Neural control
 Neural input
to
hypothalam
us
stimulates
synthesis
and
secretion of
releasing
factors
which
stimulate
pituitary
hormone
production
and release

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 Feedback control
Negative feedback is most common:
for example, LH from pituitary
stimulates the testis to produce
testosterone which in turn feeds back
and inhibits LH secretion
Positive feedback is less common:
examples include LH stimulation of
estrogen which stimulates LH surge at
ovulation
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Negative feedback effects of cortisol

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 Substrate-hormone control
Glucose and insulin: as glucose
increases it stimulates the
pancreas to secrete insulin

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 Feedback control of insulin by
glucose concentrations

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