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Endocrine System: General Principles in Endocrinology On the other hand, epinephrine is not an example of this

(Gloria Marie M. Valerio, MD) because it is synthesized by adrenal medulla but it is not synthesized in
the sympathetic nerve endings. The formation of epinephrine from
Endocrine System Nervous System norepinephrine takes place only in the adrenal medulla because the
enzyme that will catalyze this reaction is present only in the adrenal
Hormones Nerve impulses medulla that is why there is no conversion of epinephrine from
norepinephrine int the sympathetic post ganglionic nerve endings. So
Circulation Faster/Localized epinephrine is a hormone.
Slower/Diffused
3. Neuroendocrine Hormones
Regulate body processes
These are chemical substances synthesized by neuroendocrine
In the body there are two systems that regulate the different cells but released into the blood and NOT in the synaptic cleft. There are
body functions or processes and these are the endocrine system and two hormones synthesized by hypothalamic nuclei, stored and released
nervous system. These two systems aside from regulating different body by the posterior pituitary gland into the circulating blood and these are
processes or functions can also provide a means of communication oxytocin and the antidiuretic hormone (ADH).
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 4. Paracrine
respond.
Paracrines are also hormones. It is synthesized by an
The endocrine system can regulate body functions or endocrine gland but released only into the interstitial fluid and NOT in
processes by releasing chemical substances called hormones into the the circulating blood. The target cell is located near the secretory cell. We
different body fluids and when we say body fluids we mean circulating will talk more about the paracrine control system when we go to the
blood and interstitial fluid. So from the body fluids, hormones are actions of insulin and glucagon.
transported to a specific site where they act on specific target cell eliciting
a physiologic response from the target cell. Regulation of the different 5. Autocrine
body processes by the endocrine system is said to be slower but more
diffuse. Slower, meaning the latent period or the interval between These are also chemical substances released into the
hormoneal stimulation and target cell response is longer. Diffuse because interstitial fluid. They act on the same cell that will synthesize them.
there are some hormones that can act on several target cells at the same Example is tumor growth factor (TGF). Tumour cells secrete a growth
time. factor into the interstitial fluid and this growth factor will act on the same
tumour cell stimulating growth of the tumour cell.
On the other hand, the nervous system regulates body
functions or processes by generating action potentials or nerve impulses 6. Cytokines
and these action potentials or nerve impulses are transmitted by specific
efferent or motor neuron to specific target cell or effector cell again These are peptides synthesized and released by the cells of the
eliciting a physiologic response from the target cell. And transmission of immune system and their main function is to mediate the actions of the
impulses from a motor neuron to an effector or target cell is also cells of the immune system.
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 Different Body Functions or Processes Regulated by the Endocrine
cell response is shorter. Localized because remember that specific motor System
neuron will innervate only specific effector cell.
1. Chemical Homeostasis
These are the two systems that regulate the different body
functions or processes and one thing common to both system is their Protein metabolism
actions are mediated by chemical substances; hormones for the Carbohydrate metabolism
endocrine system, neurotransmitter agent for the nervous system. Fat metabolism
Water and electrolyte metabolism

Types of Chemical Messenger System (Mediators) Under this, we have regulation of carbohydrate, fat and protein
metabolism. To give you examples of hormones that regulate
1. Neurotransmitters carbohydrate, fat and protein metabolism, we have insulin and glucagon
from the pancreatic islets of Langerhans; growth hormone from the
Examples are acetylcholine and norepinephrine. How would anterior pituitary gland; even thyroid hormones from the thyroid gland;
you classify a chemical substance as a neurotransmitter agent? First, it has cortisol from the adrenal cortex; epinephrine and norepinephrine from
to be synthesized in the axon terminal of a neuron. Next, its release is due the adrenal medulla.
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 Next, still under chemical homeostasis is regulation of water
is facilitated by calcium ions. and electrolyte metabolism. Hormones involved are ADH from the
posterior pituitary gland, parathyroid hormone (PTH) from the
2. Endocrine Hormones parathyroid gland and aldosterone from the adrenal cortex.

This is also a chemical substance this time synthesized by 2. Reproduction


endocrine glands. Upon stimulation, they are released into the body fluids
mostly into the circulating blood and an endocrine hormone will act on a Reproduction is completely dependent on the endocrine
target cell that is located far from the secretory cell. That is why it system and this will involve the actions of sex hormones like estrogen
circulates first because the target cell is far from the secretory cell. Can a and progesterone from the ovaries, testosterone from the testes.
hormone be a neurotransmitter agent or a neurotransmitter agent be a
hormone? Yes, example is norepinephrine. Remember that 3. Growth
norepinephrine is synthesized by sympathetic post ganglionic nerve
endings and at the same time it is also synthesized by a gland which is the In relation to growth, the endocrine system can stimulate
adrenal medulla. cellular growth, division, differentiation as well as metabolism. Examples

1 Shannen Kaye B. Apolinario, RMT


of hormones that stimulate growth are growth hormone from the 3. Thyroid Gland T3, T4, Calcitonin
anterior pituitary gland and thyroid hormones from the thyroid gland.
Even insulin, estrogen, progesterone, testosterone can all stimulate There are two types of secretory cells in the thyroid gland.
cellular growth. 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.
4. Behavior Then we have the parafollicular cells that secrete calcitonin and the major
target organ of calcitonin is the bone.
There are some behavioural patterns that can also be
influenced by specific hormones. For example, in patients under 4. Parathyroid Gland - PTH
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 Parathyroid glands secrete the parathyroid hormone. Target
stressful condition because the adrenal medulla is stimulated to increase organs of PTH are the bone, intesinte, kidneys.
the secretion of epinephrine and norepinephrine. Even cortisol, it is also
considered an anti-stress hormone. 5. Islets of Langerhans Insulin, Glucagon

Among the hormones secreted by the pancreatic islets are


The endocrine system has three major components. First, we insulin and glucagon. The target cells of insulin are muscle cell, adipose
have a group of secretory cells or what we call endocrine glands. When cell and liver cell. For glucagon, it has only one target organ and that is the
stimulate, they will release a chemical substance into the body fluids liver.
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 6. Adrenal Cortex MC, GC, Androgen
cells. These are the components of the endocrine system and we will now
discuss each component. 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
Classification of Endocrine Glands 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
I. Purely Endocrine glucocorticoids is cortisol. The innermost layer is the zona reticularis that
also secretes glucocorticoids and androgens but this time more of
In the body, endocrine glands are grouped into two. First, we androgens than glucocorticoids.
have what we call purely endocrine glands. Purely endocrine because
their only function is endocrine and that is to secrete hormones. 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
1. Anterior Pituitary Gland (Adenohypophysis) GH, PrL, cells of the body specially the cells of the immune system. When we say
TSH, ACTH, FSH, LH androgenic hormones, these are hormones with masculinising effects.

Among the hormones secreted by the anterior pituitary gland 7. Adrenal Medulla EP, NEP
are growth hormone (GH) or somatotropin or somatotrophic hormone,
prolactin (PrL) or lactotrophic hormone, thyroid stimulating hormone Adrenal medulla secretes catecholamines epinephrine and
(TSH) or thyrotropin, adrenocorticotropic hormone (ACTH) or norepinephrine. These catecholamines can also act on almost all cells of
corticotrophin, two types of gonadotrophic hormones or gonatropins: the body.
follicle stimulating hormone (FSH), luteinizing hormone (LH).
8. Ovaries Estrogen, Progesterone
The target cells or organs of each hormone:
Growth hormone - among its many target organs are the liver, In females, ovaries secrete estrogen and progesterone. These
bone, muscle soft tissue. two hormones regulate the female reproductive function. Its target organ
Prolactin mammary gland is the female reproductive organs
Thyrotropin thyroid gland
Corticotrophin adrenal cortex 9. Testes Testosterone
FSH and LH ovaries in females, testis in males
In males, the testes secrete testosterone. Testosterone
Take note that these hormones are called trophic hormones. regulates the male reproductive function and its target organ is the male
Trophic, meaning to say, they can stimulate growth as well as secretory reproductive organs.
activity of their respective target glands or target organs. If you notice,
these trophic hormones can actually regulate the functions of almost all Why are the ovaries and testes included as part of purely
the other endocrine glands in the body so that when we say master endocrine glands but it has gametogenic functions? Its gametogenic
gland, we refer to the anterior pituitary gland. functions are completely dependent on the hormones.

2. Posterior Pituitary Gland (Neurohypophysis) - ADH,


Oxytocin II. Partly Endocrine

Take note the posterior pituitary gland does NOT synthesize Aside from secreting hormones, they can serve other functions.
any hormones. Its major function is to store and release hormones that
are synthesized by hypothalamic nuclei. Again, there are two hormones 1. Nerve Endings Ach, EP
synthesized by hypothalamic nuclei, stored and released by the posterior
pituitary gland. First is antidiuretic hormone (ADH) or arginine Nerve endings release acetylcholine and norepinephrine.
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 2. GIT Gastrin, CCK, Secretin
muscular layer of the uterus or myometrium and myoepithelial cells of
the breasts. Also considered a partly endocrine organ is the
gastrointestinal tract. Remember that the mucosal glands in the GIT can

2 Shannen Kaye B. Apolinario, RMT


secrete many hormones and the most predominant are gastrin, Hypothalamus
cholecystokinin and secretin.
RH/RF
Gastrin stimulates secretion of hydrochloric acid (HCl) by the H-H Portal Vessels IH/IF
parietal cells on the stomach for the conversion of pepsinogen to pepsin,
increases gatric motility for increased gastric emptying, stimulates Anterior Pituitary Posterior Pituitary
growth of the gastric mucosa, stimulates insulin and glucagon secretion,
stimulates contraction of the lower esophageal sphincter. Physiologically, the pituitary gland is divided into two parts.
80% of the pituitary gland is the anterior pituitary gland or
Cholecystokinin (CCK) stimulates the contraction of adenohypophyis and the remaining 20% is the posterior pituitary gland
gallbladder, relaxation of sphincter of Oddi for the release of bile to the or neurohypophyisis. In between, there is the parts intermedia which in
duodenum, stimulates secretion of enterokinase, stimulates the pancreas human beings is avascualar or no blood supply so it has no function. We
to release digestive enzymes from the acinar cells. also mentioned that the hormones secreted by the anterior pituitary
gland can regulate the functions of almost all the other endocrine glands
Secretin stimulates the pancreatic ductal cells to secrete in the body that is why it is called the master gland. But the main
alkaline fluid rich in bicarbonate. activity of the anterior and posterior pituitary gland is regulated by a
higher center which is the hypothalamus.
3. Kidneys Erythropoietin, Vit. D
There is a network of blood vessels connecting the
The kidneys secrete two hormones: erythropoietin and the hypothalamus to the anterior and posterior pituitary glands and we call
active form of vitamin D. The target organ of erythropoietin is the bone this the hypothalamic-hypophyseal portal vessels. In addition, the
marrow. The target organs of vitamin D are the same as in PTH bone, posterior pituitary gland is actually an outgrowth of the hypothalamus so
intestine and kidneys. 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
4. Placenta - HCG and neural. How does the hypothalamus regulate posterior pituitary
activity? It is also neural. Nerve impulses can be transmitted by nerve
During pregnancy it is the placenta that secretes the hormones tracts to the posterior pituitary gland and that will stimulate the posterior
of pregnancy that will include the human chorionic gonadotropin (HCG). pituitary gland. Vascular-neural connection, neural regulation.

In the anterior pituitary gland, vascular connection. The


5. Heart ANP
hypothalamus regulate anterior pituitary activity is through hormonal
regulation. The hypothalamus can secrete releasing hormones or
The atrial muscle cells secrete atrial natriuretci peptide. The
releasing factors into the hypothalamic-hypophyseal portal vessels and
target cell of ANP is the DCT for natriuresis. Its secretion is stimulated if
these releasing hormones will then be transported to the anterior
there is increased in blood volume in the right atrium when there is
pituitary gland where they will act on specific cells of the anterior
increased venous return.
pituitary to cause the secretion of specific trophic hormones. Also, the
hypothalamus can secrete inhibitory hormones or inhibitory factors this
6. Skin Melanin time inhibiting specific cells in the anterior pituitary gland from secreting
specific trophic hormones. Vascular connection, hormonal regulation.
In the skin, we have the melanocytes that secrete melanin for
increased skin pigmentation.
Hormones Secreted by the Hypothalamus
7. Liver IGF, VIt. D
1. GHRH (Somatotropin Releasing Factor) (+) GH. Growth
One of the hormones or protein mediators secreted by the liver hormone releasing hormone or somatotropin releasing factor
is what we call insulin-like growth factor (IGF) or somatomedin. There stimulates secretion of growth hormone
are several types however insulin-like growth factor I (IGF I) or
somatomedin C mediates the actions of growth hormone related to 2. GHIH (Somatostatin) (-) GH. Growth hormone inhibitory
growth. The liver can also produce several form of vitamin D but they are hormone or somatostatin inhibit growth hormone secretion.
less active than the one produced by the kidneys.
3. PIH (-) PrL. Prolactin inhibitory hormone which is said to
be the same as dopamine so it will inhibit prolactin secretion.
8. Pineal Gland Melatonin
4. PRH (+) PrL. Prolactin releasing hormone that will
Pineal gland secretes melatonin. Melatonin is synthesized from stimulate prolactin secretion.
serotonin. The synthesis of melatonin follows a cyclic process. It is
stimulated by darkness but inhibited by light so that means that 5. TRH (+) TSH, PrL. Thyrotropin releasing hormone can
melatonin can actually transmit signals that will inform the center that stimulate secretion not only of thyrotropin or TSH but also of
night time has arrived so that the different body processes can be prolactin.
regulated accordingly. Also, melatonin is said to induce sleep,
6. CRH (+) ACTH, MSH. Corticotropin releasing hormone
stimulates the secretion of ACTH or coticotropin. But take note
9. Hypothalamus in the anterior pituitary gland, the cells that secrete
corticotropin can secrete another substance which is
Aside from endocrine function, the thirst center, satiety center structurally related to corticotropin and that is the melanocyte
(main ganglion of autonomics), temperature regulation are all located in stimulating hormone. But in human beings, there is more ACTH
the hypothalamus. 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.

3 Shannen Kaye B. Apolinario, RMT


*** 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 The neurotransmitters released either into the neuromuscular
hormones cannot cross the cell membrane and it cannot be given orally or neuroeffector junction also act locally because remember at the
(e.g. insulin) because it will be digested by the GI enzymes. neuromuscular or neuroeffector junction, the axon terminals are close to
the membrane of the effector cell.
2. Biogenic Amines
T3, T4 2. General Hormones
EP, NEP Site of effect is distant from site of release
PIF (Dopamine) Examples: thyroid hormones, growth hormones, trophic
hormones from adenohypophysis
Hormones that are synthesized from the amino acid tyrosine
are classified as biogenic amines and this will include the thyroid General hormones are hormones that act on target cells that
hormones - T3, T4, catecholamines epinephrine and norepinephrine, as are located far from the secretory cell. They are released in the blood, it
well as the prolactin inhibitory factor or dopamine. has to be transported in a distant site from the secretory cell.

T3 and T4 are synthesized by the thyroid follicular cells. After Examples are thyroid hormones. From the thyroid gland in the
synthesis, they are stored temporarily in the lumen of the thyroid follicle neck, thyroid hormones can act on the heart, they can act on the bone and
bound to a large glycoprotein molecule that is thyroglobulin. Just like the muscle, it can act on the GIT and all are far from the thyroid gland.
protein or polypeptide hormones, the secretion of T3 and T4 is not Another example is growth hormone from the anterior pituitary gland, it
continuous. It is only secreted upon stimulation so they can be stored. will act on the liver in the abdominal cavity, bone, muscle, all of which are
They are also released by exocytosis into the circulating blood and this far from the anterior pituitary gland. Also, the trophic hormones from
time, 99% of circulating thyroid hormones are bound to plasma proteins anterior pituitary gland, example is TSH. So from the anterior pituitary
and only 1% is free. Since many are bound to plasma proteins, its half life gland, it has to be transported in the thyroid gland. ACTH from the
is long. Thyroid hormones can cross the cell membrane. anterior pituitary gland, it has to be transported to the adrenal glands. So
the target cells are far from the secretory cells.
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 Mechanism of Action of a Hormone
synthesized in the adrenal medulla. In the circulating blood, they are
present in two forms, either bound or loosely bound to albumin and they 1. Hormone-Receptor Interaction
cannot cross the cell membrane. Receptors:
o Are chemical agents
3. Steroid o Stereospecificity
Estrogen, Progesterone, Testosterone o Number can increase of decrease; can even disappear
Cortisol, Aldosterone, Androgens Up-regulation = increase in one hormone can
Vitamin D increase number of receptors
Down-regulation
Hormones that are synthesized from cholesterol are classified
as steroid hormones and this will include sex hormones, adrenocortical Before a hormone can act on a target cell, it has to bind with
hormones and vitamin D. This time, they are lipid soluble so they are not receptors in the target cell so you need a hormone-receptor interaction or
soluble in the circulating blood. Again, they are present in the circulating a hormone-receptor complex. What are receptors? They are chemical
blood mostly bound to plasma proteins so its half life is long but they are subunits most of them are proteins and one important property of these
not stored in the secretory cells so whatever amount that is synthesized receptors is stereospecificty. It means that the configuration of one
are also released. Since they are lipid soluble, they can readily cross the receptor can only match to the configuration of one hormone. So the
cell membrane. 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.
III. Classification According to the Site of Target Cell
Since these receptors are proteins, they can be degraded or
1. Local Hormone resynthesized so that their number in the target cell is not constant. It can
Site of effect is close to site of release either increase or decrease or the receptors may disappear from the
Examples: target cell. Once its number decreased or disappeared, even if there are
o Paracrine system of pancreatic islet cells plenty of hormones there will be no action in the target cell. Example:
Beta cells (-) alpha cells there are two types of diabetes mellitus 1 and 2. In type 1, there is
(insulin) (glucagon) destruction of the pancreatic cells thus there is really no insulin so that
Alpha cells (+) beta cells the blood glucose level continues to increase. In type 2, the pancreatic B
(glucagon) (insulin) cells are normal or sometimes insulin secretion is higher than normal but
o NTA Ach and NEP the blood glucose level keeps on getting higher because the receptors
either decreased or disappeared on the target cell.
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 Increased estrogen Increased production of receptors Oxytocin
hormones.
In relation to this, we have the principle of up-regulation of
Also included is the paracrine control system that exists in the receptors. Up-regulation wherein if there is an increase in one hormone,
pancreatic islets of Langerhans. So in the pancreatic islets there are this can up-regulate or increase the number of receptors for itself or for
different types of secretory cells secreting different types of hormones. another hormone. For example, if hormone A increased, in up-regulation,
What can happen is that insulin secreted by the cells can inhibit cells it will also increase receptors for itself or for other hormones. Another
from secreting glucagon. It is adjacent to one another so insulin can be example is during the last trimester of pregnancy, that is where the
released in the interstitial fluid and not in the blood. Same thing with secretion of estrogen is highest and one important action of estrogen is to
glucagon from the cells can stimulate cells to secrete insulin. So they increase the production of receptors for oxytocin in the myometrium of
are adjacent to each other and it is only in the interstitial fluid where the the uterus. So that once the posterior pituitary gland secreted oxytocin, it
hormones are released. 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

5 Shannen Kaye B. Apolinario, RMT


unless the uterus has been exposed to a large amount of estrogen so activation of G-proteins on the inner surface of the membrane. Activated
oxytocin can actually stimulate contraction of an estrogen-primed uterus. G-proteins will activate an intracellular enzyme, in this case it is adenylyl
It is estrogen that will stimulate the production of receptors for oxytocin. 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
Increased progesterone > Increased estrogen another intracellular enzyme that is protein kinase that will cause
phosphorylation of specific intracellular proteins and this will now lead
Decreased receptor for estrogen to stimulation of specific biochemical intracellular reactions. When this
happens, this could lead to the opening of ion channels, stimulate gene
On the other hand, sometimes if there are excessive amount of transcription, formation of intracellular proteins, all of which will change
hormone, a large amount will bind to the receptor so the receptor is the metabolic set-up of the cell allowing the cell to respond to the
desensitized or destroyed it is down regulated. Excess hormones can presence of a hormone.
now decrease the receptors in the target cell for itself or for another
hormone. Example, during the post-ovulatory phase of the female Hormones that use Adenylyl cyclase cAMP system
monthly cycle the predominant hormone secreted is progesterone CRH, GHIH
although you still have estrogen. One action of estrogen is to stimulate the ACTH, FSH, LH, TSH
innermost layer of the uterus called endometrium to proliferate. When HCG, PTH, Calcitonin
the concentration of progesterone increases, it down-regulates the ADH (V2 receptors in the DCT)
receptors for estrogen so receptors for estrogen in the endometrium is Catecholamines ( receptors)
decreased so even if you have estrogen, it cannot stimulate endometrial Angiotensin II (epithelial cells in renal tubules)
proliferation and the endometrial thickening stops. Glucagon

b. Phospholipid 2nd messenger system


Hormone-Receptor Interaction
H + receptor activate G-proteinl (+) phospholipase C
Location of Receptors: Breakdown of P1P2
Cell membrane
o Protein IP3 DAG
o Peptide
o Catecholamines Inc. IC Ca++ (+) PKC
Cytoplasm
o Steroid Phosphorylates protein
Nucleus
o T3, T4 This time again a hormone will bind with a receptor on the
outer surface of the membrane activating G-proteins. Activated G-
There are receptors located in the plasma or cell membrane of proteins will now activate another enzyme system that is phospholipase
the target cell and that is where protein or polypeptide hormones as well C that will cause breakdown of phosphoinositol biphosphate (P1P2). One
as catecholamines bind to. Or in other words, the receptors for protein or of the breakdown products of P1P2 is inositol triphosphate (IP3) and
polypeptide hormones as well as for catecholamines are located in the presence of IP3 increases intracellular calcium. Calcium by itself can
cell membrane because remember that they cannot cross the cell function as a 2nd messenger. The other breakdown product of P1P2 is
membrane. For steroid hormones which are lipid soluble, they can readily diacylglycerol (DAG), DAG stimulates protein kinase C that will again
cross the cell membrane, bind with intracellular or cytoplasmic receptors. cause phosphorylation of specific intracellular proteins that will stimulate
Thyroid hormones on the other hand bind with nuclear receptors. specific biochemical intracellular reactions.

Membrane Receptors Hormones that use Phospholipase C 2nd messenger system


GnRH, GHRH, TRH
1. Ion channel linked receptors Oxytocin
ADH (V1 receptor in the vascular smooth muscle)
H + receptor open ion channels Catecholamines ( receptor)
A II (vascular smooth muscle)
Ion channel linked receptors or simply known as ligand gated
ion channels. For example, acetylcholine when it binds with a nicotinic
c. Calcium-Calmodulin 2nd messenger system. These are
receptor on the membrane of the skeletal muscle cell, that will open up present in the visceral smooth muscle.
sodium channels allowing Na influx, depolarizing the membrane, exciting
the effector cell. Steroid hormones are lipid-soluble
2. G-protein couple receptor 2nd messenger mechanism Cross the cell membrane readily
a. Adenylyl cyclase cAMP
Interact with cytoplasmic receptors
H + R activate G-protein (+) adenylyl cyclase cAMP (+) protein
Steroid-receptor complex enters the nucleus
kinase phosphorylate specific IC proteins (+) biochemical reaction
in the cell
(+) specific DNAs
The other type of membrane receptors are G-protein coupled
Production of specific mRNAs
receptors. Receptors are located on the outer surface of the membrane
while G-proteins are on the inner surface of the membrane. Activation of Inc. synthesis of specific IC enzymes
G-proteins will lead to the production of intracellular ligands or what we
call second messengers. This second messengers will mediate the action Mechanism action of steroid hormones: they are lipid soluble,
of the hormone on the target cell. they can readily cross the cell membrane and bind with cytoplasmic
receptors and the steroid hormone receptor complex will then enter the
What are the different types of second messengers? First we
nucleus of the cell this time stimulating specific DNAs that will lead to the
have the adenylyl cyclise cyclic AMP system. A hormone will bind to the
formation of specific messenger RNAs. The messenger RNAs will move
receptor on the outer surface of the membrane and that will cause

6 Shannen Kaye B. Apolinario, RMT


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