Endocrine System: General Principles in Endocrinology
(Gloria Marie M. Valerio, MD)
Endocrine System Nervous System
Hormones Nerve impulses
Circulation Faster/Localized
Slower/Diffused
Regulate body processes
In the body there are two systems that regulate the different
body functions or processes and these are the endocrine system and
nervous system. These two systems aside from regulating different body
processes or functions can also provide a means of communication
among the different cells of the body. Meaning to say, they enable signals
from one cell to be transmitted to another cell causing that cell to
respond.
The endocrine system can regulate body functions or
processes by releasing chemical substances called hormones into the
different body fluids and when we say body fluids we mean circulating
blood and interstitial fluid. So from the body fluids, hormones are
transported to a specific site where they act on specific target cell eliciting
a physiologic response from the target cell. Regulation of the different
body processes by the endocrine system is said to be slower but more
diffuse. Slower, meaning the latent period or the interval between
hormoneal stimulation and target cell response is longer. Diffuse because
there are some hormones that can act on several target cells at the same
time.
On the other hand, the nervous system regulates body
functions or processes by generating action potentials or nerve impulses
and these action potentials or nerve impulses are transmitted by specific
efferent or motor neuron to specific target cell or effector cell again
eliciting a physiologic response from the target cell. And transmission of
impulses from a motor neuron to an effector or target cell is also
mediated by a chemical substance this time we have a neurotransmitter
agent. Now regulation of body processes by the nervous system is faster.
Faster meaning the latent period between nervous stimulation and target
cell response is shorter. Localized because remember that specific motor
neuron will innervate only specific effector cell.
These are the two systems that regulate the different body
functions or processes and one thing common to both system is their
actions are mediated by chemical substances; hormones for the
endocrine system, neurotransmitter agent for the nervous system.
Types of Chemical Messenger System (Mediators)
1. Neurotransmitters
Examples are acetylcholine and norepinephrine. How would
you classify a chemical substance as a neurotransmitter agent? First, it has
to be synthesized in the axon terminal of a neuron. Next, its release is due
to an action potential or nerve impulse reaching the axon terminal. The
release of the NTA is by exocytosis into the synaptic cleft and exocytosis
is facilitated by calcium ions.
2. Endocrine Hormones
This is also a chemical substance this time synthesized by
endocrine glands. Upon stimulation, they are released into the body fluids
mostly into the circulating blood and an endocrine hormone will act on a
target cell that is located far from the secretory cell. That is why it
circulates first because the target cell is far from the secretory cell. Can a
hormone be a neurotransmitter agent or a neurotransmitter agent be a
hormone? Yes, example is norepinephrine. Remember that
norepinephrine is synthesized by sympathetic post ganglionic nerve
endings and at the same time it is also synthesized by a gland which is the
adrenal medulla.
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On the other hand, epinephrine is not an example of this
because it is synthesized by adrenal medulla but it is not synthesized in
the sympathetic nerve endings. The formation of epinephrine from
norepinephrine takes place only in the adrenal medulla because the
enzyme that will catalyze this reaction is present only in the adrenal
medulla that is why there is no conversion of epinephrine from
norepinephrine int the sympathetic post ganglionic nerve endings. So
epinephrine is a hormone.
3. Neuroendocrine Hormones
These are chemical substances synthesized by neuroendocrine
cells but released into the blood and NOT in the synaptic cleft. There are
two hormones synthesized by hypothalamic nuclei, stored and released
by the posterior pituitary gland into the circulating blood and these are
oxytocin and the antidiuretic hormone (ADH).
4. Paracrine
Paracrines are also hormones. It is synthesized by an
endocrine gland but released only into the interstitial fluid and NOT in
the circulating blood. The target cell is located near the secretory cell. We
will talk more about the paracrine control system when we go to the
actions of insulin and glucagon.
5. Autocrine
These are also chemical substances released into the
interstitial fluid. They act on the same cell that will synthesize them.
Example is tumor growth factor (TGF). Tumour cells secrete a growth
factor into the interstitial fluid and this growth factor will act on the same
tumour cell stimulating growth of the tumour cell.
6. Cytokines
These are peptides synthesized and released by the cells of the
immune system and their main function is to mediate the actions of the
cells of the immune system.
Different Body Functions or Processes Regulated by the Endocrine
System
1. Chemical Homeostasis
Protein metabolism
Carbohydrate metabolism
Fat metabolism
Water and electrolyte metabolism
Under this, we have regulation of carbohydrate, fat and protein
metabolism. To give you examples of hormones that regulate
carbohydrate, fat and protein metabolism, we have insulin and glucagon
from the pancreatic islets of Langerhans; growth hormone from the
anterior pituitary gland; even thyroid hormones from the thyroid gland;
cortisol from the adrenal cortex; epinephrine and norepinephrine from
the adrenal medulla.
Next, still under chemical homeostasis is regulation of water
and electrolyte metabolism. Hormones involved are ADH from the
posterior pituitary gland, parathyroid hormone (PTH) from the
parathyroid gland and aldosterone from the adrenal cortex.
2. Reproduction
Reproduction is completely dependent on the endocrine
system and this will involve the actions of sex hormones like estrogen
and progesterone from the ovaries, testosterone from the testes.
3. Growth
In relation to growth, the endocrine system can stimulate
cellular growth, division, differentiation as well as metabolism. Examples
of hormones that stimulate growth are growth hormone from the
anterior pituitary gland and thyroid hormones from the thyroid gland.
Even insulin, estrogen, progesterone, testosterone can all stimulate
cellular growth.
4. Behavior
There are some behavioural patterns that can also be
influenced by specific hormones. For example, in patients under
prolonged corticosteroid therapy, this may induce on the patient a manic
depressive type of behaviour. In times of stress, you are able to cope with
stressful condition because the adrenal medulla is stimulated to increase
the secretion of epinephrine and norepinephrine. Even cortisol, it is also
considered an anti-stress hormone.
The endocrine system has three major components. First, we
have a group of secretory cells or what we call endocrine glands. When
stimulate, they will release a chemical substance into the body fluids
mainly into the circulating blood and that is a hormone. This hormone
will be transported to a specific site where it will act on specific target
cells. These are the components of the endocrine system and we will now
discuss each component.
Classification of Endocrine Glands
I. Purely Endocrine
In the body, endocrine glands are grouped into two. First, we
have what we call purely endocrine glands. Purely endocrine because
their only function is endocrine and that is to secrete hormones.
1. Anterior Pituitary Gland (Adenohypophysis) GH, PrL,
TSH, ACTH, FSH, LH
Among the hormones secreted by the anterior pituitary gland
are growth hormone (GH) or somatotropin or somatotrophic hormone,
prolactin (PrL) or lactotrophic hormone, thyroid stimulating hormone
(TSH) or thyrotropin, adrenocorticotropic hormone (ACTH) or
corticotrophin, two types of gonadotrophic hormones or gonatropins:
follicle stimulating hormone (FSH), luteinizing hormone (LH).
The target cells or organs of each hormone:
Growth hormone - among its many target organs are the liver,
bone, muscle soft tissue.
Prolactin mammary gland
Thyrotropin thyroid gland
Corticotrophin adrenal cortex
FSH and LH ovaries in females, testis in males
Take note that these hormones are called trophic hormones.
Trophic, meaning to say, they can stimulate growth as well as secretory
activity of their respective target glands or target organs. If you notice,
these trophic hormones can actually regulate the functions of almost all
the other endocrine glands in the body so that when we say master
gland, we refer to the anterior pituitary gland.
2. Posterior Pituitary Gland (Neurohypophysis) - ADH,
Oxytocin
Take note the posterior pituitary gland does NOT synthesize
any hormones. Its major function is to store and release hormones that
are synthesized by hypothalamic nuclei. Again, there are two hormones
synthesized by hypothalamic nuclei, stored and released by the posterior
pituitary gland. First is antidiuretic hormone (ADH) or arginine
vasopressin. The target cells of ADH are DCT and collecting ducts of the
nephron and vascular smooth muscle. The target cells of oxytocin are the
muscular layer of the uterus or myometrium and myoepithelial cells of
the breasts.
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3. Thyroid Gland T3, T4, Calcitonin
There are two types of secretory cells in the thyroid gland.
First, we have the follicular cells that secrete the thyroid hormones T3
and T4. These thyroid hormones can act on almost all cells of the body.
Then we have the parafollicular cells that secrete calcitonin and the major
target organ of calcitonin is the bone.
4. Parathyroid Gland - PTH
Parathyroid glands secrete the parathyroid hormone. Target
organs of PTH are the bone, intesinte, kidneys.
5. Islets of Langerhans Insulin, Glucagon
Among the hormones secreted by the pancreatic islets are
insulin and glucagon. The target cells of insulin are muscle cell, adipose
cell and liver cell. For glucagon, it has only one target organ and that is the
liver.
6. Adrenal Cortex MC, GC, Androgen
The adrenal cortex is divided into three layers, each layer
secreting a different type of hormone. The outermost layer is the zona
glomerulosa that secretes mineralocorticoids. The most predominant of
the mineralocorticoids is aldosterone. The middle layer is the zona
fasciculata that secretes glucocorticoids as well as androgens (more of
glucocorticoids that androgens). The most predominant of the
glucocorticoids is cortisol. The innermost layer is the zona reticularis that
also secretes glucocorticoids and androgens but this time more of
androgens than glucocorticoids.
The target cells of aldosterone are the DCT, collecting ducts of
the nephron. As for cortisol, just like T3 and T4, it can act on almost all
cells of the body specially the cells of the immune system. When we say
androgenic hormones, these are hormones with masculinising effects.
7. Adrenal Medulla EP, NEP
Adrenal medulla secretes catecholamines epinephrine and
norepinephrine. These catecholamines can also act on almost all cells of
the body.
8. Ovaries Estrogen, Progesterone
In females, ovaries secrete estrogen and progesterone. These
two hormones regulate the female reproductive function. Its target organ
is the female reproductive organs
9. Testes Testosterone
In males, the testes secrete testosterone. Testosterone
regulates the male reproductive function and its target organ is the male
reproductive organs.
Why are the ovaries and testes included as part of purely
endocrine glands but it has gametogenic functions? Its gametogenic
functions are completely dependent on the hormones.
II. Partly Endocrine
Aside from secreting hormones, they can serve other functions.
1. Nerve Endings Ach, EP
Nerve endings release acetylcholine and norepinephrine.
2. GIT Gastrin, CCK, Secretin
Also considered a partly endocrine organ is the
gastrointestinal tract. Remember that the mucosal glands in the GIT can
secrete many hormones and the most predominant are gastrin,
cholecystokinin and secretin.
Gastrin stimulates secretion of hydrochloric acid (HCl) by the
parietal cells on the stomach for the conversion of pepsinogen to pepsin,
increases gatric motility for increased gastric emptying, stimulates
growth of the gastric mucosa, stimulates insulin and glucagon secretion,
stimulates contraction of the lower esophageal sphincter.
Cholecystokinin (CCK) stimulates the contraction of
gallbladder, relaxation of sphincter of Oddi for the release of bile to the
duodenum, stimulates secretion of enterokinase, stimulates the pancreas
to release digestive enzymes from the acinar cells.
Secretin stimulates the pancreatic ductal cells to secrete
alkaline fluid rich in bicarbonate.
3. Kidneys Erythropoietin, Vit. D
The kidneys secrete two hormones: erythropoietin and the
active form of vitamin D. The target organ of erythropoietin is the bone
marrow. The target organs of vitamin D are the same as in PTH bone,
intestine and kidneys.
4. Placenta - HCG
During pregnancy it is the placenta that secretes the hormones
of pregnancy that will include the human chorionic gonadotropin (HCG).
5. Heart ANP
The atrial muscle cells secrete atrial natriuretci peptide. The
target cell of ANP is the DCT for natriuresis. Its secretion is stimulated if
there is increased in blood volume in the right atrium when there is
increased venous return.
6. Skin Melanin
In the skin, we have the melanocytes that secrete melanin for
increased skin pigmentation.
7. Liver IGF, VIt. D
One of the hormones or protein mediators secreted by the liver
is what we call insulin-like growth factor (IGF) or somatomedin. There
are several types however insulin-like growth factor I (IGF I) or
somatomedin C mediates the actions of growth hormone related to
growth. The liver can also produce several form of vitamin D but they are
less active than the one produced by the kidneys.
8. Pineal Gland Melatonin
Pineal gland secretes melatonin. Melatonin is synthesized from
serotonin. The synthesis of melatonin follows a cyclic process. It is
stimulated by darkness but inhibited by light so that means that
melatonin can actually transmit signals that will inform the center that
night time has arrived so that the different body processes can be
regulated accordingly. Also, melatonin is said to induce sleep,
9. Hypothalamus
Aside from endocrine function, the thirst center, satiety center
(main ganglion of autonomics), temperature regulation are all located in
the hypothalamus.
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Hypothalamus
RH/RF
H-H Portal Vessels IH/IF
Anterior Pituitary Posterior Pituitary
Physiologically, the pituitary gland is divided into two parts.
80% of the pituitary gland is the anterior pituitary gland or
adenohypophyis and the remaining 20% is the posterior pituitary gland
or neurohypophyisis. In between, there is the parts intermedia which in
human beings is avascualar or no blood supply so it has no function. We
also mentioned that the hormones secreted by the anterior pituitary
gland can regulate the functions of almost all the other endocrine glands
in the body that is why it is called the master gland. But the main
activity of the anterior and posterior pituitary gland is regulated by a
higher center which is the hypothalamus.
There is a network of blood vessels connecting the
hypothalamus to the anterior and posterior pituitary glands and we call
this the hypothalamic-hypophyseal portal vessels. In addition, the
posterior pituitary gland is actually an outgrowth of the hypothalamus so
there are nerve tracts that will connect the hypothalamus to the posterior
pituitary gland. So the connection is vascular and on the other is vascular
and neural. How does the hypothalamus regulate posterior pituitary
activity? It is also neural. Nerve impulses can be transmitted by nerve
tracts to the posterior pituitary gland and that will stimulate the posterior
pituitary gland. Vascular-neural connection, neural regulation.
In the anterior pituitary gland, vascular connection. The
hypothalamus regulate anterior pituitary activity is through hormonal
regulation. The hypothalamus can secrete releasing hormones or
releasing factors into the hypothalamic-hypophyseal portal vessels and
these releasing hormones will then be transported to the anterior
pituitary gland where they will act on specific cells of the anterior
pituitary to cause the secretion of specific trophic hormones. Also, the
hypothalamus can secrete inhibitory hormones or inhibitory factors this
time inhibiting specific cells in the anterior pituitary gland from secreting
specific trophic hormones. Vascular connection, hormonal regulation.
Hormones Secreted by the Hypothalamus
1. GHRH (Somatotropin Releasing Factor) (+) GH. Growth
hormone releasing hormone or somatotropin releasing factor
stimulates secretion of growth hormone
2. GHIH (Somatostatin) (-) GH. Growth hormone inhibitory
hormone or somatostatin inhibit growth hormone secretion.
3. PIH (-) PrL. Prolactin inhibitory hormone which is said to
be the same as dopamine so it will inhibit prolactin secretion.
4. PRH (+) PrL. Prolactin releasing hormone that will
stimulate prolactin secretion.
5. TRH (+) TSH, PrL. Thyrotropin releasing hormone can
stimulate secretion not only of thyrotropin or TSH but also of
prolactin.
6. CRH (+) ACTH, MSH. Corticotropin releasing hormone
stimulates the secretion of ACTH or coticotropin. But take note
in the anterior pituitary gland, the cells that secrete
corticotropin can secrete another substance which is
structurally related to corticotropin and that is the melanocyte
stimulating hormone. But in human beings, there is more ACTH
than MSH. Both of them have a hyperpigmenting action.
7. GnRH (+) FSH, LH. Gonadotropin releasing hormone will
stimulate the secretion of the two types of gonadotropins: LH
and FSH.
*** Remember the abbreviations because its name already indicates its bind with receptor. If it is bound to a protein, it cannot bind to the
action. If it is releasing hormone, it is from the hypothalamus while receptor.
stimulating or trophic hormones is from the anterior pituitary gland.
Protein bound hormones are inactive but it has three uses.
Protein binding can prolong plasma half-life a hormone. Protein binding
will facilitate the transport of a hormone to the target cell. And it also acts
Hormones
as a reservoir, meaning to say, when the free hormone has already been
utilized by the target cell, it can be unbound from protein binding
I. General Characteristics
converting it into an active form.
1. Secreted by a specific group of cells
The binding proteins are produced by the liver and estrogen
can actually stimulate the liver to stimulate the production of binding
Hormones are chemical substances secreted by specific group
proteins.
of secretory cells or what we call endocrine glands.
In the plasma, an equilibrium exists between proein bound
2. Thrown directly into circulation and other body fluids
hormone and free hormone. For example, there is excess free hormone,
the excess will bind to plasma protein so that will render the hormone
As differentiated from exocrine glands, endocrine glands are
inactive and that will prevent overstimulation or over-activity of the
ductless so that the hormones or their secretory products are thrown
target cell. On the other hand, when the active hormone has been used up,
directly into the body fluids mostly into the circulating blood.
the free or active hormone concentration will decrease, protein bound
hormones will unbound making it active so that will prevent
hypostimulation or hypo-activity of the target cell.
3. Do not create additional function in the body
7. Main site of inactivation: liver
We mentioned that the main function of the endocrine system
is to regulate body processes or functions. Take note that they regulate
While there are some hormones that can be inactivated in the
existing body functions or processes. They do not create a new function in
target cell, most of the inactivation takes place in the liver.
the cell, they do not add another function to the cell, they only regulate
existing body functions and that is done by acting on the different
8. Removal from the circulation
intracellular metabolic enzymes. Hormones can either increase or
decrease the synthesis as well as activity of the different intracellular
The products of hormone inactivation are cleared from the
enzymes and therefore can either increase or decrease the rate of existing
plasma through the kidneys.
chemical processes in the cell.

What is the difference between a hormone and an enzyme? Both

II. Classification According to Chemical Composition
are chemical substances. Enzymes will catalyze the chemical reaction and
the hormone will act on the enzyme.
1. Polypeptide
Hypothalamic hormones
Is renin a hormone, an enzyme or both? According to Dra.
Anterior / Posterior pituitary hormones
Viliran, it is very controversial. It cannot be classified if it is a hormone, an
enzyme or both. PTH, Calcitonin
Insulin, Glucagon
4. Onset and duration of action
What is the difference between a polypeptide and a protein?
As to onset and duration of action, we already mentioned that Protein is larger because it is made up of several polypeptides.
in the endocrine or hormonal system, the latent period is longer.
However, once the target cell responds to the hormone, the duration of Hypothalamic hormones: releasing hormones and inhibitory
the response is also longer. hormones from the hypothalamus EXCEPT for dopamine. Anterior
pituitary hormones or the trophic hormones but take note there are three
5. Plasma concentration anterior pituitary hormones that are not purely proteins instead they are
glycoproteins and these are TSH, FSH and LH. Then you have ADH and
In the circulating blood, hormones are present in low oxytocin from the posterior pituitary gland, PTH, calcitonin, insulin and
concentration. In fact you need only a small amount of a hormone to glucagon. So these are polypeptide or protein hormones.
stimulate the target cell.
[Synthesized in the RER]
6. Transport Preprohormone

Blood = 2 forms Pro-hormone

Active hormone
Protein-bound Free
(inactive) (active) What are the characteristics or properties of polypeptide or
protein hormones? In the secretory cells, they are synthesized in the
Liver binding proteins rough endoplasmic reticulum from a large precursor called a
preprohormone. A preprohormone is cleaved to form a smaller
Estrogen (+) liver inc. production of binding proteins
molecule which is now called a prohormone. Usually they are not
Excess free hormone protein-binding inc. inactive
released into the circulating blood and they are inactive. A prohormone
Dec. free hormone protein bound hormones are
will be cleaved to form a smaller molecule which is now the active
released
hormone and this active hormone will be stored temporarily in secretory
vesicles released only upon stimulation. So it means that protein
In the circulating blood, hormones are present in two forms,
hormones can be stored and its secretion is not continuous, only upon
either they are protein bound or free. Protein bound hormone is
stimulation. Secretion is also by exocytosis, facilitated by calcium ion. In
biologically inactive. It is the free hormone that is biologically active.
the circulating blood, protein or polypeptide hormones are soluble so
Protein bound hormones are inactive because it cannot pass through the
they are transported mainly in the unbound form and since they are
cell membrane and before a hormone can act on its target cell, it has to
4 Shannen Kaye B. Apolinario, RMT
unbound, its plasma half life is shorter. Also, protein or polypeptide
hormones cannot cross the cell membrane and it cannot be given orally
(e.g. insulin) because it will be digested by the GI enzymes.
2. Biogenic Amines
T3, T4
EP, NEP
PIF (Dopamine)
Hormones that are synthesized from the amino acid tyrosine
are classified as biogenic amines and this will include the thyroid
hormones - T3, T4, catecholamines epinephrine and norepinephrine, as
well as the prolactin inhibitory factor or dopamine.
T3 and T4 are synthesized by the thyroid follicular cells. After
synthesis, they are stored temporarily in the lumen of the thyroid follicle
bound to a large glycoprotein molecule that is thyroglobulin. Just like the
protein or polypeptide hormones, the secretion of T3 and T4 is not
continuous. It is only secreted upon stimulation so they can be stored.
They are also released by exocytosis into the circulating blood and this
time, 99% of circulating thyroid hormones are bound to plasma proteins
and only 1% is free. Since many are bound to plasma proteins, its half life
is long. Thyroid hormones can cross the cell membrane.
The secretory product of adrenal medulla is 80% epinephrine,
20% norepinephrine and a very small amount of dopamine. So this PIF or
dopamine is not synthesize in the hypothalamus only, it is also
synthesized in the adrenal medulla. In the circulating blood, they are
present in two forms, either bound or loosely bound to albumin and they
cannot cross the cell membrane.
3. Steroid
Estrogen, Progesterone, Testosterone
Cortisol, Aldosterone, Androgens
Vitamin D
Hormones that are synthesized from cholesterol are classified
as steroid hormones and this will include sex hormones, adrenocortical
hormones and vitamin D. This time, they are lipid soluble so they are not
soluble in the circulating blood. Again, they are present in the circulating
blood mostly bound to plasma proteins so its half life is long but they are
not stored in the secretory cells so whatever amount that is synthesized
are also released. Since they are lipid soluble, they can readily cross the
cell membrane.
III. Classification According to the Site of Target Cell
1. Local Hormone
Site of effect is close to site of release
Examples:
o Paracrine system of pancreatic islet cells
Beta cells (-) alpha cells
(insulin) (glucagon)
Alpha cells (+) beta cells
(glucagon) (insulin)
o NTA Ach and NEP
If the target cell is located near the secretory cell, we call the
hormone released as a local hormone. Most of the GI hormones are local
hormones.
Also included is the paracrine control system that exists in the
pancreatic islets of Langerhans. So in the pancreatic islets there are
different types of secretory cells secreting different types of hormones.
What can happen is that insulin secreted by the cells can inhibit cells
from secreting glucagon. It is adjacent to one another so insulin can be
released in the interstitial fluid and not in the blood. Same thing with
glucagon from the cells can stimulate cells to secrete insulin. So they
are adjacent to each other and it is only in the interstitial fluid where the
hormones are released.
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The neurotransmitters released either into the neuromuscular
or neuroeffector junction also act locally because remember at the
neuromuscular or neuroeffector junction, the axon terminals are close to
the membrane of the effector cell.
2. General Hormones
Site of effect is distant from site of release
Examples: thyroid hormones, growth hormones, trophic
hormones from adenohypophysis
General hormones are hormones that act on target cells that
are located far from the secretory cell. They are released in the blood, it
has to be transported in a distant site from the secretory cell.
Examples are thyroid hormones. From the thyroid gland in the
neck, thyroid hormones can act on the heart, they can act on the bone and
muscle, it can act on the GIT and all are far from the thyroid gland.
Another example is growth hormone from the anterior pituitary gland, it
will act on the liver in the abdominal cavity, bone, muscle, all of which are
far from the anterior pituitary gland. Also, the trophic hormones from
anterior pituitary gland, example is TSH. So from the anterior pituitary
gland, it has to be transported in the thyroid gland. ACTH from the
anterior pituitary gland, it has to be transported to the adrenal glands. So
the target cells are far from the secretory cells.
Mechanism of Action of a Hormone
1. Hormone-Receptor Interaction
Receptors:
o Are chemical agents
o Stereospecificity
o Number can increase of decrease; can even disappear
Up-regulation = increase in one hormone can
increase number of receptors
Down-regulation
Before a hormone can act on a target cell, it has to bind with
receptors in the target cell so you need a hormone-receptor interaction or
a hormone-receptor complex. What are receptors? They are chemical
subunits most of them are proteins and one important property of these
receptors is stereospecificty. It means that the configuration of one
receptor can only match to the configuration of one hormone. So the
receptor for estrogen cannot bind with progesterone, receptor for T3
cannot bind with PTH, receptor with insuin cannot bind with glucagon so
the hormone-receptor interaction is very specific.
Since these receptors are proteins, they can be degraded or
resynthesized so that their number in the target cell is not constant. It can
either increase or decrease or the receptors may disappear from the
target cell. Once its number decreased or disappeared, even if there are
plenty of hormones there will be no action in the target cell. Example:
there are two types of diabetes mellitus 1 and 2. In type 1, there is
destruction of the pancreatic cells thus there is really no insulin so that
the blood glucose level continues to increase. In type 2, the pancreatic B
cells are normal or sometimes insulin secretion is higher than normal but
the blood glucose level keeps on getting higher because the receptors
either decreased or disappeared on the target cell.
Increased estrogen Increased production of receptors Oxytocin
In relation to this, we have the principle of up-regulation of
receptors. Up-regulation wherein if there is an increase in one hormone,
this can up-regulate or increase the number of receptors for itself or for
another hormone. For example, if hormone A increased, in up-regulation,
it will also increase receptors for itself or for other hormones. Another
example is during the last trimester of pregnancy, that is where the
secretion of estrogen is highest and one important action of estrogen is to
increase the production of receptors for oxytocin in the myometrium of
the uterus. So that once the posterior pituitary gland secreted oxytocin, it
will now bind with the receptors in the myometrium and it can stimulate
uterine contractions. One action of oxytocin is to stimulate uterine
contraction but oxytocin per se cannot stimulate uterine contraction
unless the uterus has been exposed to a large amount of estrogen so
oxytocin can actually stimulate contraction of an estrogen-primed uterus.
It is estrogen that will stimulate the production of receptors for oxytocin.
Increased progesterone > Increased estrogen
Decreased receptor for estrogen
On the other hand, sometimes if there are excessive amount of
hormone, a large amount will bind to the receptor so the receptor is
desensitized or destroyed it is down regulated. Excess hormones can
now decrease the receptors in the target cell for itself or for another
hormone. Example, during the post-ovulatory phase of the female
monthly cycle the predominant hormone secreted is progesterone
although you still have estrogen. One action of estrogen is to stimulate the
innermost layer of the uterus called endometrium to proliferate. When
the concentration of progesterone increases, it down-regulates the
receptors for estrogen so receptors for estrogen in the endometrium is
decreased so even if you have estrogen, it cannot stimulate endometrial
proliferation and the endometrial thickening stops.
Hormone-Receptor Interaction
Location of Receptors:
Cell membrane
o Protein
o Peptide
o Catecholamines
Cytoplasm
o Steroid
Nucleus
o T3, T4
There are receptors located in the plasma or cell membrane of
the target cell and that is where protein or polypeptide hormones as well
as catecholamines bind to. Or in other words, the receptors for protein or
polypeptide hormones as well as for catecholamines are located in the
cell membrane because remember that they cannot cross the cell
membrane. For steroid hormones which are lipid soluble, they can readily
cross the cell membrane, bind with intracellular or cytoplasmic receptors.
Thyroid hormones on the other hand bind with nuclear receptors.
Membrane Receptors
1. Ion channel linked receptors
H + receptor open ion channels
Ion channel linked receptors or simply known as ligand gated
ion channels. For example, acetylcholine when it binds with a nicotinic
receptor on the membrane of the skeletal muscle cell, that will open up
sodium channels allowing Na influx, depolarizing the membrane, exciting
the effector cell.
2. G-protein couple receptor 2nd messenger mechanism
a. Adenylyl cyclase cAMP
H + R activate G-protein (+) adenylyl cyclase cAMP (+) protein
kinase phosphorylate specific IC proteins (+) biochemical reaction
in the cell
The other type of membrane receptors are G-protein coupled
receptors. Receptors are located on the outer surface of the membrane
while G-proteins are on the inner surface of the membrane. Activation of
G-proteins will lead to the production of intracellular ligands or what we
call second messengers. This second messengers will mediate the action
of the hormone on the target cell.
What are the different types of second messengers? First we
have the adenylyl cyclise cyclic AMP system. A hormone will bind to the
receptor on the outer surface of the membrane and that will cause
6 Shannen Kaye B. Apolinario, RMT
activation of G-proteins on the inner surface of the membrane. Activated
G-proteins will activate an intracellular enzyme, in this case it is adenylyl
cyclise that will lead to the formation of cAMP. cAMP is the intracellular
ligand or the 2nd messenger. The first action of cAMP is to activate
another intracellular enzyme that is protein kinase that will cause
phosphorylation of specific intracellular proteins and this will now lead
to stimulation of specific biochemical intracellular reactions. When this
happens, this could lead to the opening of ion channels, stimulate gene
transcription, formation of intracellular proteins, all of which will change
the metabolic set-up of the cell allowing the cell to respond to the
presence of a hormone.
Hormones that use Adenylyl cyclase cAMP system
CRH, GHIH
ACTH, FSH, LH, TSH
HCG, PTH, Calcitonin
ADH (V2 receptors in the DCT)
Catecholamines ( receptors)
Angiotensin II (epithelial cells in renal tubules)
Glucagon
b. Phospholipid 2nd messenger system
H + receptor activate G-proteinl (+) phospholipase C
Breakdown of P1P2
IP3 DAG
Inc. IC Ca++ (+) PKC
Phosphorylates protein
This time again a hormone will bind with a receptor on the
outer surface of the membrane activating G-proteins. Activated G-
proteins will now activate another enzyme system that is phospholipase
C that will cause breakdown of phosphoinositol biphosphate (P1P2). One
of the breakdown products of P1P2 is inositol triphosphate (IP3) and
presence of IP3 increases intracellular calcium. Calcium by itself can
function as a 2nd messenger. The other breakdown product of P1P2 is
diacylglycerol (DAG), DAG stimulates protein kinase C that will again
cause phosphorylation of specific intracellular proteins that will stimulate
specific biochemical intracellular reactions.
Hormones that use Phospholipase C 2nd messenger system
GnRH, GHRH, TRH
Oxytocin
ADH (V1 receptor in the vascular smooth muscle)
Catecholamines ( receptor)
A II (vascular smooth muscle)
c. Calcium-Calmodulin 2nd messenger system. These are
present in the visceral smooth muscle.
Steroid hormones are lipid-soluble
Cross the cell membrane readily
Interact with cytoplasmic receptors
Steroid-receptor complex enters the nucleus
(+) specific DNAs
Production of specific mRNAs
Inc. synthesis of specific IC enzymes
Mechanism action of steroid hormones: they are lipid soluble,
they can readily cross the cell membrane and bind with cytoplasmic
receptors and the steroid hormone receptor complex will then enter the
nucleus of the cell this time stimulating specific DNAs that will lead to the
formation of specific messenger RNAs. The messenger RNAs will move
out of the nucleus, stimulate the ribosomes to increase the synthesis of H CRH
specific intracellular protein enzymes. (+)
AP ACTH
T3 and T4 Interact w/ nuclear receptor
Aderenla cortex
(+) specific DNAs
Cortisol, Androgens
Production of specific mRNAs
Not all layers of adrenal cortex is dependent on ACTH. The
Inc. synthesis of IC enzymes hypothalamus will secrete corticotrophin releasing hormone that will
stimulate the anterior pituitary gland to secrete corticotropin or ACTH.
T3 and T4 bind with nuclear receptors again stimulation The zona glomerulosa is ACTH is independent, only the zona fasciculata
specific DNAs that will cause the production of specific RNAs. This RNAs and zona reticularis are ACTH dependent. (Aldosterone secretion is not
will then move out of the nucleus to stimulate the ribosomes to increase dependent on ACTH. The major factor that regulates the secretion of
the synthesis of intracellular enzymes. aldosterone is K and RAAS). It stimulates the adrenal cortex but only the
two layers and there will be secretion of cortisol and androgenic
Steroid hormones and thyroid hormones can stimulate gene hormones.
transcription: it simulates DNA and produces mRNA so we can consider
these hormones as gene stimulators. So when we say gene stimulators, H GnRH
they are steroid and thyroid hormones. (+)
AP

Regulation of Endocrine Secretion FSH LH

1. Indirect Nervous Control H-H target gland axis Ovary

Hypothalamus RF/RH Estrogen Progesterone

(+)
AP trophic hormone In females, hypothalamus secretes gonadotropin releasing
(+) hormone that will stimulate the anterior pituitary gland to secrete FSH
Target gland hormones and LH. The target gland is the ovary. The ovary will secrete estrogen and
progesterone. The cells that produce estrogen and progesterone are
True for AP, thyroid, adrenal cortex, ovaries, testes different.

One mechanism that regulates endocrine function is indirect H GnRH

nervous control via the hypothalamic-hypophyseal target gland axis. The (+)
hypothalamus secretes a releasing factor or releasing hormone that will AP
stimulate specific cells of the anterior pituitary gland to secrete specific
trophic hormone. This trophic hormone will act on a specific target gland FSH LH
to cause the secretion of a hormone that is why it is called hypothalamic-
hypophyseal target gland. Sertoli cell ICL

This is the mechanism that will regulate the activity of the Inhibin Testosterone
anterior pituitary gland, thyroid, adrenal cortex, ovaries, and testis.
In males, hypothalamus secretes gonadotropin releasing
H hormone that will stimulate the anterior pituitary gland to secrete FSH
and LH. The target gland is the testis. In the testis, FSH stimulates the
GHRH GHIH sertoli cells so there will be secretion of a little amount of estrogen and
(+) (-) another hormone that is inhibin. LH stimulates the interstial cells of
AP Leydig that will secrete testosterone.

GH
Regulation of Hormone Secretion
Liver IGF-I
a. Negative feedback control
The hypothalamus secretes the growth hormone releasing
hormone that will stimulate the anterior pituitary gland to secrete growth Excess free hormone from a target gland will inhibit the
hormone. One of the target cell or target organ of growth hormone is the hypothalamus and anterior pituitary gland.
liver. When stimulated, it will produce IGF I or somatomedin C. But
remember that the hypothalamus can also stimulate the secretion of H
growth inhibitory hormone that will now inhibit the anterior pituitary
gland from secreting growth hormone. GHRH GHIH (-)
(+) (-)
H TRH AP
(+)
AP TSH GH (-)

Thyroid gland T3, T4 Liver Inc. IGF-I

The hypothalamus secretes thyrotropin releasing hormone IGF I can regulate GHRH and GH by exerting a negative
that will stimulate the anterior pituitary gland to secrete thyrotropin. feedback effect that is if it is in excess, it inhibits the hypothalamus from
Target gland now is the thyroid gland. When stimulated by TSH, it will secreting GHRH, it inhibits the anterior pituitary gland from producing
release T3 and T4. growth hormone. Everything will decrease and it will return back to

7 Shannen Kaye B. Apolinario, RMT

normal. If it go beyond the normal, negative feedback will stop so it will
increase again. Estrogen also has a positive feedback effect. Excess free
hormone from a target gland will further stimulate the hypothalamus and
H TRH (-) long loop anterior pituitary gland. That is exemplified by an excessive increase in
estrogen secretion a few hours before ovulation. So if there is excess in
AP TSH (-) short loop estrogen, positive feedback is activated to the hypothalamus and anterior
pituitary gland resulting to further increase in GnRH, FSH, LH and
Thyroid gland T3, T4 estrogen. Excessive increase in estrogen is the only one that has a positive
feedback.
If you have TRH, you will have TSH, T3 and T4. If there is an
excess free T3, T4, negative feedback will be activated resulting to a
decrease in TRH, TSH. If the negative feedback is exerted on the anterior In relation to this, you have to know the three levels:
pituitary gland, it is the short loop. If it goes to the hypothalamus, it is the hypothalamus, anterior pituitary gland and target gland. In endocrine
long loop. system disorders, there are three types: primary, secondary and tertiary.
If the disorder is primary, the defect is in the target gland. If it is
H CRH secondary, the problem is in the anterior pituitary gland. If it is tertiary,
the problem is in the hypothalamus. So the hormonal pictures are
AP ACTH (-) different depending on the condition.

Aderenla cortex (-) T3, T4 TSH TRH

1o hypothyroidism Decreased Increased Increased
Cortisol, Androgens
2o hypothyroidism Decreased Decreased Increased
3o hypothyroidism Decreased Decreased Decreased
Between cortisol and androgens, it is mainly the excess in free
cortisol that will have a feedback effect because the androgens produced 1o hyperthyroidism Increased Decreased Decreased
by the adrenal cortex are weak so if you have excess cortisol, negative 2o hyperthyroidism Increased Increased Decreased
feedback will be activated decreased CRH, decreased ACTH. 3o hyperthyroidism Increased Increased Increased

H GnRH Example, if a patient has primary hypothyroidism, the problem

is in the thyroid gland so there is no production of T3 and T4. TRH will
AP (-) now increase because there is no negative feedback. TSH will also
increase because there is no negative feedback. Comparing it to
FSH LH secondary hypothyroidism or pituitary hypothyroidism, the first one to
(-) decrease is TSH. Because there is no TSH, T3 and T4 will also decrease
Ovary but TRH will increase since there is no negative feedback. But if it is
tertiary hypothyroidism, TRH, TSH, T3 and T4 are all decreased.
Estrogen Progesterone
In primary hyperthyroidism, you have increase T3 and T4 so
In females, increased progesterone will activate negative negative feedback is activated so there is decrease in TRH and TSH. If it is
feedback going to the anterior pituitary gland but the main effect is in LH secondary or pituitary hyperthyroidism, there is increase in TSH, increase
secretion. If there is a moderate increase in estrogen which will happen in T3 and T4, decreased TRH. If it is tertiary hyperthyroidism, increased
at the beginning of the female monthly cycle, negative feedback will be TRH, TSH, T3 and T4.
activated but in the anterior pituitary gland, mainly in the FSH.
2. Modified Negative Feedback Control
H GnRH Independent of the hypothalamus and anterior pituitary gland
(+) Negative feedback is not due to excess hormone from a target
AP (-) gland but to a blood metabolite regulated by the hormone
True for: PTH, islet of Langerhan, adrenal cortex (aldosterone)
FSH LH
(-) Decreased calcium
(-) Sertoli cell ICL
PTH
Inhibin Testosterone (-)
Bone Intestine Kidney
In males, increased testosterone activates the negative
feedback anterior pituitary gland, mainly LH. It is an increase in inhibin Increased Calcium
that will have a negative feedback in FSH anterior pituitary gland only
so it is short loop. Another mechanism outside of the H-H target gland axis is the
modified negative feedback. According to Berne and Levy, it is called the
b. Positive Feedback Control physiologic response driven feedback. This mechanism can regulate
Excess free hormone from a target gland stimulates the hormonal activity without the involvement of hypothalamus and anterior
hypothalamus and anterior pituitary gland pituitary gland. You have a negative feedback effect that is not exerted by
a hormone but it is exerted by a metabolite in the blood. But the blood
H GnRH concentration of that metabolite is regulated by a hormone and this type
(+) of mechanism will regulate the activity of the following glands: PTH, islets
AP of Langerhan and adenal cortex (aldosterone).

FSH LH Parathyroid. Hypocalcemia is the major stimulus that will

cause the secretion of parathyroid hormone. PTH acts on three target
Ovary organs: bone, intestine and kidneys and the net effect is to cause
hypercalcemia. Hypercalcemia will inhibit further PTH secretion. So you
Estrogen Progesterone have a negative feedback effect wherein hypothalamus and anterior
pituitary gland are not involved and the negative feedback is exerted not

8 Shannen Kaye B. Apolinario, RMT

by a hormone but by a metabolite in the blood, in this case it is calcium.
Calcium will inhibit PTH secretion but the plasma calcium level is
regulated by PTH.

Insulin and glucagon. The metabolite is blood glucose. If the

blood glucose is high, insulin secretion is stimulated to decrease blood
glucose level. If it is already low, insulin secretion is inhibited.
In aldosterone, it is mainly hyperkalemia. If potassium is
increased, aldosterone is secreted to remove potassium thereby
decreasing it.

3. Permissive Action of a Hormone

PTH Inc. Vitamin D Inc. intestinal absorption of Ca

Another mechanism is permissive action of a hormone. This

time, hormone A does not act directly on the target cell. Instead, hormone
A increases the production of hormone B and hormone B will act on the
target cell. So hormone A indirectly acts on the target cell and has a
permissive action on hormone B.

Example, in parathyroid hormone, we mentioned that one of

its target cells is the gastrointestinal tract but is indirect. It can increase
intestinal absorption of calcium by increasing the production of active
vitamin D. It is vitamin D that will directly increase intestinal absorption
of calcium. So PTH indirectly increases intestinal absorption of calcium
and PTH has a permissive action on vitamin D.

4. Direct Nervous Control

Sympathetic preganglionic fibers
(+)
Adrenal medullary cells
(+)
Secretion of catecholamines

Impulses from hypothalamus

(+)
Posterior pituitary gland
(+)
Release of stored ADH (oxytocin)

There are two endocrine glands whose activities are under

direct nervous or neural control: adrenal medulla and posterior pituitary
gland. Remember there are some sympathetic pre-ganglionic fibers that
will synapse with the adrenal medullary cells and the adrenal medullary
cells are histologically similar to a sympathetic ganglion so that when the
sympathetic nervous system is stimulated, the adrenal medulla is also
stimulated to release epinephrine and norepinephrine.

The other one is the posterior pituitary gland which is an

outgrowth of the hypothalamus so that nerve impulses from the
hypothalamus will be transmitted by nerve fibers to the posterior
pituitary gland and that will cause the release of either ADH or oxytocin.

This is the confidence we have in approaching God: that if we ask

anything according to His will, He hears us. And if we know that He
hears us whatever we ask we know that we have what we asked
of Him.
-1 John 5: 14, 15

GOD BLESS YOU

9 Shannen Kaye B. Apolinario, RMT