Physiology

Semester
Introduction to Endocrine System
Valerio, MD | 28 03 2018
 Faster: the latent period between
OUTLINE nervous stimulation and target cell
I. Endocrine System and Nervous System response is shorter
II. Types of Chemical Messenger System (Mediators)  Localized: the specific motor neuron
III. Different Body Functions or Processes Regulated by the will innervate only specific effector cell
Endocrine System  One thing in common to both systems: actions are
IV. Components of Endocrine System mediated by chemical substances
V. Classification of Endocrine Glands o Endocrine: hormones
A. Purely Endocrine o Nervous: neurotransmitters
B. Partly Endocrine
VI. Hormones
A. General Characteristics
B. Classification According to Chemical Composition
C. Classification According to the Site of Target Cell
VII. Mechanism of Action of A Hormone
VIII. Hormone-Receptor Interaction
A. Membrane Receptors
Fig 1. Endocrine System and Nervous System
IX. Regulation of Endocrine Secretion
A. Regulation of Hormone Secretion
Table 1. Nervous System vs Endocrine System
NERVOUS ENDOCRINE
I. ENDOCRINE SYSTEM AND NERVOUS SYSTEM Chemical
Neurotransmitters Hormones
 There are two systems that regulate the different body Substance
functions or processes, also they provide a means of
communication among different cells of the body Regulation Faster, localized Slower, diffuse
o Endocrine system
o Nervous system
 These systems enable signals from one cell to be II. TYPES OF CHEMICAL MESSENGER SYSTEM (MEDIATORS)
transmitted to another cell causing cell to respond
 Endocrine System  Neurotransmitters
o Regulate body functions or processes by releasing o Examples: Ach, NE
chemical substances called hormones into the o Synthesized in the axon terminal of a neuron
different body fluids (circulating blood and o Its release is due to an action potential or nerve
interstitial fluid) impulse reaching the axon terminal
o Hormones are transported to a specific site where o The release of the NTA is by exocytosis into the
they act on specific target cell, eliciting a synaptic cleft, which is facilitated by calcium ions
physiologic response from the target cell  Endocrine Hormones
o Regulation of the different body processes by o Synthesized by endocrine glands
endocrine system is said to be slower, but more o Upon stimulation, they are released into the
diffuse body fluids mostly into the circulating blood and
 Slower: the latent period or the interval an endocrine hormone will act in a target cell
between hormonal stimulation and that is located far from the secretory cell – it
target cell response is longer circulates first because the target cell is far from
 Diffuse: there are some hormones that the secretory cell
can act on several target cells at the o Can a hormone be a neurotransmitter or a
same time neurotransmitter agent be a hormone? Yes.
 Nervous System Example, norepinephrine – it is synthesized by
o Regulates body functions or processes by sympathetic postganglionic nerve endings and at
generating action potentials or nerve impulses the same time it is also synthesized by a gland
which are transmitted by specific efferent or (adrenal medulla)
motor neuron to specific target cell or effector o Epinephrine is not an example of this because it
cell is synthesized by adrenal medulla and it is not
o This is mediated by a chemical substance called synthesized in the sympathetic nerve endings,
neurotransmitter also the formation or epinephrine from
o Regulation of body processes by the nervous norepinephrine takes place only in the adrenal
system is faster and localized medulla because the enzyme that will catalyse
this reaction is present only in the adrenal

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 Physiology
Introduction to Endocrine System
medulla and not in the postganglionic nerve  Growth
endings; therefore, epinephrine is a hormone o Endocrine system can stimulate cellular growth,
 Neuroendocrine Hormones division, differentiation as well as metabolism
o These are synthesized by neuroendocrine cells o Examples
but released into the blood and not in the  Growth hormone from the anterior
synaptic cleft pituitary gland
o Oxytocin and antidiuretic hormone (ADH) are  Thyroid hormones from the thyroid
hormones synthesized by hypothalamic nuclei, gland
stored and released by the posterior pituitary  Insulin, estrogen, progesterone,
gland into the circulating blood testosterone – can stimulate cellular
 Paracrine growth
o Paracrines are also hormones  Behavior
o It is synthesized by an endocrine gland but o There are some behavioural patterns that can
released only into the interstitial fluid and not in also be influenced by specific hormones
the circulating blood  Patients under prolonged
o The target cell is located near the secretory cell corticosteroid therapy may have a
o Example: insulin and glucagon manic depressive type of behaviour
 Autocrine  In times of stress, you are able to cope
o These are also chemical substances released into with stressful condition because the
the interstitial fluid adrenal medulla is stimulated to
o They act on the same cell that will synthesize increase the secretion of epinephrine
them and norepinephrine
o Example: tumor growth factor (TGF), in which  Cortisol is also considered an anti-
tumor cells secrete a growth factor into the stress hormone
interstitial fluid and this growth factor will act on
the same tumor cell stimulating growth of the IV. COMPONENTS OF ENDOCRINE SYSTEM
tumor cell
 Three major components
 Cytokines
o Group of secretory cells or what we call
o These are peptides synthesized and released by
endocrine glands
the cells of the immune system
o Hormone – a chemical substance released into
o Main function: mediate the actions of the cell of
the body fluids
the immune system
o Specific target cells
III. DIFFERENT BODY FUNCTIONS OR PROCESSES REGULATED BY THE
V. CLASSIFICATION OF ENDOCRINE GLANDS
ENDOCRINE SYSTEM
 Purely Endocrine – their only function is endocrine and
 Chemical Homeostasis
that is to secrete hormones
o Protein, carbohydrate, fat, water, and electrolyte
 Partly Endocrine – aside from secreting hormones, they
metabolism
can serve other functions
o Carbohydrate, fat, and protein metabolism
 Insulin and glucagon from the
A. PURELY ENDOCRINE
pancreatic islets of Langerhans
1. Anterior Pituitary Gland (Adenohypophysis)
 Growth hormone from the anterior
 Hormones secreted
pituitary gland
o Growth hormone (GH) or somatotropin or
 Thyroid hormones from thyroid gland
somatotrophic hormone
 Cortisol from the adrenal cortex
o Prolactin (PrL) or lactotrophic hormone
 Epinephrine and norepinephrine from
o Thyroid stimulating hormone (TSH) or thyrotropin
the adrenal medulla
o Adrenocorticotropic hormone (ACTH) or
o Water and electrolyte metabolism
corticotrophin
 ADH from the posterior pituitary gland
o Gonadotrophic hormones or gonatropins (two
 Parathyroid hormone (PTH) from the
types): follicle stimulating hormone (FSH) and
parathyroid gland
luteinizing hormone (LH)
 Aldosterone from adrenal cortex
 These hormones are called trophic hormones
 Reproduction
o Meaning, they can stimulate growth as well as
o It is completely dependent on the endocrine
secretory activity of their respective target glands
system
or target organs
o Involves the actions of sex hormones like
o They can actually regulate the functions of almost
estrogen and progesterone from ovaries,
all the other endocrine glands in the body so that
testosterone from the testes

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when we say master gland, we refer to the  Target organs of PTH
anterior pituitary gland o Bone
o Intestines
Table 2. Hormones in the Anterior Pituitary Gland and Their Target o Kidneys
Cells or Organs
HORMONE TARGET CELLS OR ORGANS 5. Islets of Langerhans
 Hormones
Growth Hormone Liver, bone, muscle soft tissue o Insulin
o Glucagon

Prolactin Mammary gland Table 5. Islets of Langerhans Hormones

HORMONE TARGET CELLS OR ORGANS

Thyrotropin Thyroid gland Insulin Muscle cells, adipose cells, liver cells

Corticotrophin Adrenal Cortex

Glucagon Liver

FSH and LH Ovaries, testis

6. Adrenal Cortex
 Hormones
2. Posterior Pituitary Gland (Neurohypophysis) o Mineralocorticoids
 Hormones associated with posterior pituitary gland o Glucocorticoids
o Antidiuretic Hormone (ADH) or arginine o Androgens
vasopressin  Adrenal cortex is divided into three layers, each of which
o Oxytocin secretes different type of hormone
 Posterior pituitary gland does not synthesize any hormones o Zona glomerulosa: outermost
 Its major function is to store and release hormones that are o Zona fasciculate: middle
synthesized by hypothalamic nuclei o Zona reticularis: innermost
 Target cells
Table 3. Hormones in the Posterior Pituitary Gland and Their Target o Aldosterone: DCT, collecting ducts of nephron
Cells or Organs o Cortisol: act on almost all cells of the body
HORMONE TARGET CELLS OR ORGANS especially the cells of the immune system
 Androgenic hormones have masculinising effects
DCT and collecting ducts of nephron,
ADH
vascular smooth muscle
Table 6. Hormones of Adrenal Cortex
Muscular layer of the ZONES HORMONES
Oxytocin uterus/myometrium, and
myoepithelial cells of the breasts Mineralocorticoids (most predominant is
Zona glomerulosa
aldosterone)
3. Thyroid Gland
 Hormones Zona fasciculata Glucocorticoids > androgens
o T3
o T4
o Calcitonin Zona reticularis Glucocorticoids < androgens

Table 4. Hormones of Thyroid Gland

7. Adrenal Medulla
SECRETORY HORMONES TARGET CELLS OR
 Hormones
CELLS ORGANS
o Epinephrine
Act on almost all cells o Norepinephrine
Follicular Cells T3, T4  Target cells
of the body
o Almost all cells of the body
Parafollicular
Calcitonin Bone 8. Ovaries
cells
 Hormones
o Estrogen
4.Parathyroid Gland o Progesterone
 Hormone: PTH

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 Function of hormones: regulate female reproductive HORMONE TARGET CELLS OR ORGANS
function
 Target organ: female reproductive organs Vitamin D Bone, intestine, kidneys

9. Testes
4. Placenta
 Hormone: testosterone
 During pregnancy, it is the placenta that secretes the
 Function: Regulates male reproductive function
hormones of pregnancy that will include human chorionic
 Target organ: Male reproductive organs
gonadotropin (HCG)
Why are the ovaries and testes included as part of purely endocrine
5. Heart
glands but it has gametogenic functions? Its gametoganic function are
 Hormone: atrial natriuretic peptide (ANP)
completely dependent on the hormones.
 Target cell: DCT for natriuresis
B. PARTLY ENDOCRINE  Stimulus: increased blood volume in the right atrium when
1. Nerve Endings there is increased venous return
 Nerve endings release
o Acetylcholine 6. Skin
o Norepinephrine  In the skin, we have melanocytes that secrete melanin for
increased skin pigmentation
2. GIT
 Hormones: 7. Liver
o Gastrin  Hormones
o CCK o Insulin-like growth factor (IGF) or somatomedin
o Secretin o Vitamin D
 Mucosal glands in the GIT can secrete many hormones  There are several types
 Gastrin  Insulin-like growth factor I (ICF I) or somatomedin C
o Stimulates secretion of HCl by the parietal cells on mediates actions of the growth hormone related to growth
the stomach for the conversion of pepsinogen to  Liver can also produce several forms of vitamin D but they
pepsin are less active than the one produced by the kidneys
o Increases gastric motility for increased gastric
emptying 8. Pineal Gland
o Stimulates growth of the gastric mucosa  Hormone: melatonin
o Stimulates insulin and glucagon secretion  Melatonin is synthesized from serotonin
o Stimulates contraction of the lower esophageal  The synthesis of melatonin follows a cyclic process
sphincter  It is stimulated by darkness but inhibited by light so that
 Cholecystokinin means that melatonin can actually transmit signals that will
o Stimulates contraction of the bladder inform the center that night time has arrived, so that the
o Relaxation of sphincter of Oddi for the release of different processes can be regulated accordingly
bile to the duodenum  Melatonin is said to induce sleep
o Stimulates secretion of enterokinase
o Stimulates pancreas to release digestive enzymes 6. Hypothalamus
from the acinar cells  Aside from endocrine function, the thirst center, satiety
 Secretin center (main ganglion of autonomics), temperature
o Stimulates the pancreatic ductal cells to secrete regulation are all located in the hypothalamus
alkaline fluid rich in bicarbonate

3. Kidneys
 Hormones
o Erythropoietin
o Active form of vitamin D
Fig 2. Hypothalamic-Hypophyseal Portal Vessels.
Table 7. Hormones of Kidneys
HORMONE TARGET CELLS OR ORGANS  Physiologically, the pituitary gland is divided into to parts
o 80%: anterior pituitary gland or adenohypophysis
o 20%: posterior pituitary gland or
Erythropoietin Bone marrow neurohypophysis
 In between of these two parts, there is the parts intermedia
which is avascular or has no blood supply, thus has no
function

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 The main activity of the anterior and posterior pituitary stimulating hormone; in human beings, there is
gland is regulated by a higher center which is the more ACTH than MSH – both have
hypothalamus hyperpigmenting action
 Hypothalamic-hypophyseal portal vessels: network of  GnRH → (+) FSH, LH
blood vessels connecting the hypothalamus to the anterior o Gonadotropin releasing hormone will stimulate
and posterior pituitary glands the secretion of the two types of gonadotropins:
 Posterior pituitary gland is actually an outgrowth of the LH and FSH
hypothalamus so there are nerve tracts that will connect
the hypothalamus to posterior pituitary gland IV. HORMONES
 The connection in adenohypophysis is vascular, while in A. GENERAL CHARACTERISTICS
neurohypophysis, it is vascular and neural  Secreted by a specific group of cells
 How does the hypothalamus regulate posterior pituitary o Hormones are chemical substances secreted by
activity? It is also neural specific group of secretory cells or what we call
o Nerve impulses can be transmitted by nerve endocrine glands
tracts to the posterior pituitary gland and that will  Thrown directly into circulation and other body fluids
stimulate the posterior pituitary gland o As differentiated from exocrine glands, endocrine
o Vascular-neural connection, neural regulation glands are ductless so that the hormones or their
 In the anterior pituitary gland, vascular connection secretory products are thrown directly into the
o The hypothalamus regulate anterior pituitary body fluids mostly into the circulating blood
activity through hormonal regulation  Do not create additional function in the body
o Hypothalamus can secrete releasing hormones or o The main function of the endocrine system is to
releasing factors into the hypothalamic- regulate body processes or functions
hypophyseal portal vessel and these releasing o They do not create a new function in the cell, they
hormones will then be transported to the anterior only regulate existing body functions and that is
pituitary gland where they will act on specific cells done by acting on the different intracellular
of the anterior pituitary to cause the secretion of metabolic enzymes
specific trophic hormones o Hormones can either increase or decrease the
o Hypothalamus can secrete inhibitory hormones synthesis as well as activity of the different
or inhibitory factors this time inhibiting specific intracellular enzymes and therefore can either
cell in the anterior pituitary gland from secreting increase or decrease the rate of existing chemical
specific trophic hormones processes in the cell
o Vascular connection, hormonal regulation o What is the difference between a hormone and an
enzyme? Both are chemical substances; enzyme
1.1 Hormones Secreted by the Hypothalamus will catalyse chemical reaction and hormone will
 GHRH (Somatotropin Releasing Factor) → (+) GH act on the enzyme
o Growth hormone releasing hormone or  Onset of duration of action
somatotropin releasing factor stimulates o Endocrine or hormonal system has a longer latent
secretion of growth hormone period
 GHIH (Somatostatin) → (-) GH o However, once the target cell responds to the
o Growth hormone inhibitory hormone or hormone, the duration of the response is longer
somatostatin inhibits growth hormone secretion  Plasma concentration
 PIH → (-) PrL o In the circulating blood, hormones are present in
o Prolactin inhibitory hormone which is said to be low concentration
the same as dopamine inhibits prolactin secretion o You only need a small amount of hormones to
 PRH → (+) PrL stimulate the target cell
o Prolactin releasing hormone that will stimulate  Transport
prolactin secretion o Hormones has two forms in the blood
 TRH → (+) TSH, PrL  Protein-bound (inactive, because it
o Thyrotropin releasing hormone can stimulate cannot pass through the cell membrane
secretion not only of thyrotropin or TSH but also and it cannot bind to the receptor)
of prolactin  Free (active)
 CRH → (+) ACTH, MSH o Liver → binding proteins
o Corticotropin releasing hormone stimulates the o Estrogen (+) liver → inc. production of binding
secretion of ACTH or corticotropin proteins
o Note: In the anterior pituitary gland, the cells that o Excess free hormone → protein-binding inc. →
secrete corticotropin can secrete another inactive
substance which is structurally related to o Dec. free hormone → protein bound hormones
corticotropin and that is the melanocyte are released

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o Protein bound hormones are inactive but it has  Preprohormone is cleaved to form a
three uses smaller molecule which is now called a
 Protein binding prolong plasma half-life prohormone, which are usually inactive
a hormone and are not leased into the blood
 Protein binding will facilitate the  A prohormone will be cleaved to form a
transport of a hormone to the target smaller molecule which is now the
cell active hormone, which is temporarily
 It acts as a reservoir – when the free stored in secretory vesicles and is only
hormone has already been utilized by released upon stimulation
the target cell. it can be unbound from o Protein hormones can be stored and its secretion
protein binding converting it into an is not continuous, only upon stimulation
active form o Secretion is by exocytosis, facilitated by calcium
o The binding proteins are produced by the liver ion
and estrogen can actually stimulate the liver to o In the circulating blood, protein or polypeptide
stimulate the production of binding proteins hormones are soluble – they are transported
o In plasma, an equilibrium exists between protein mainly in the unbound form, and its plasma half-
bound hormones and free hormones life is shorter
 When there is excess free hormone, the o Protein or polypeptide hormones cannot cross
excess will bind to plasma protein so the cell membrane
that will render the hormone inactive o It cannot be given orally because it will be
and that will prevent overstimulation or digested by the GI enzymes
over-activity of the target cell
 When the active hormone has been
used up, the free or active hormone
concentration will decrease, protein
bound hormones will unbound making
it active so that will prevent
hypostimulation of hypo-activity of the
target cell Fig 3. Synthesis of Hormones.
 Main site of inactivation: liver
o While there are some hormones that can be  Biogenic Amines
inactivated in the target cell, most of the o T3, T4, EP, NEP, PIF (dopamine)
inactivation takes place in the liver o Hormones that are synthesized from the amino
 Removal from the circulation acid tyrosine are classified as biogenic amines and
o The products of hormone inactivation are cleared this will include the thyroid hormones – T3, T4;
from the plasma through the kidneys catecholamines – epinephrine and
norepinephrine, as well as the prolactin inhibitory
B. CLASSIFICATION ACCORDING TO CHEMICAL COMPOSITION factor or dopamine
 Polypeptide o T3 and T4 are synthesized by the thyroid follicular
o Hypothalamic hormones, anterior/posterior cells; after synthesis, they are temporarily store in
pituitary hormones, PTH, calcitonin, insulin, the lumen of the thyroid follicle bound to a large
glucagon glycoprotein molecule called thyroglobulin
o What is the difference between a polypeptide and o T3 and T4 secretion is not continuous; it is only
a protein? Protein is larger because it is made up secreted upon stimulation so they can be stored;
of several polypeptides (>50) they are also released by exocytosis – 99% of
o Hypothalamic hormones: releasing hormones which are bound to plasma proteins, and only 1%
and inhibitory hormones from the hypothalamus is free, leading to long half-life
except for dopamine o Thyroid hormones can cross the cell membrane
o Anterior pituitary hormones or the trophic o Secretory product of adrenal medulla is 80%
hormones: take note there are three anterior epinephrine, 20% norepinephrine, and a very
pituitary hormones that are not purely proteins small amount of dopamine – they are present in
instead they are glycoproteins (TSH, FSH, and LH) two forms in the circulating blood: either bound
o Posterior pituitary gland: ADH and oxytocin or loosely bound to albumin; they cannot cross
o What are the characteristics or properties of the cell membrane
polypeptide or protein hormones?  Steroid
 In secretory cells, they are synthesized o Estrogen, progesterone, testosterone, cortisol,
in the rough ER from a large precursor aldosterone, androgens, vitamin D
called preprohormone o Hormones that are synthesized from cholesterol
are classified as steroid hormones which include

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sex hormones, adrenocortical hormones, and  Number can increase or decrease; can
vitamin D even disappear (up-regulation, increase
o They are lipid soluble so they are not soluble in in one hormone can increase number of
the circulating blood receptors; down-regulation)
o They are present in the circulating blood mostly o Before a hormone can act on a target cell, it has
bound to plasma proteins; its half-life is long, but to bind with receptors in the target cell so you
they are not stored in the secretory cells; need a hormone-receptor interaction or a
whatever amount that is synthesized are also hormone-receptor complex
released o What are receptors? They are chemical subunits,
o They can readily cross the cell membrane most of them are proteins and one important
property of these receptors is stereospecificity,
C. CLASSIFICATION ACCORDING TO THE SITE OF TARGET CELL which means that the configuration of one
 Local Hormone receptor can only match to the configuration of
o Site of effect is close to site of release one hormone; for example, receptor with insulin
o Examples: cannot bind with glucagon; hormone-receptor
 Paracrine system of pancreatic islet interaction is very specific
cells: beta cells (insulin) → (-) alpha cells o Since these receptors are proteins, they can be
(glucagon); alpha cells (glucagon) → (+) degraded or resynthesized so that their number
beta cells (insulin) in the target cell is not constant; it can either
 NTA – Ach and NEP increase or decrease or the receptors may
o Most of the GI hormones are local hormones disappear from the target cell
o Paracrine control system exists in the pancreatic o Example, there are two types of DM – 1 and 2; in
islets of Langerhans; insulin secreted by the beta type 1, there is destruction of the pancreatic beta
cells can inhibit alpha cells from secreting cells thus there is no insulin, leading to the
glucagon, because it is adjacent to one another so increase in the blood glucose level; in type 2, the
insulin can be released in the interstitial fluid and pancreatic beta cells are normal or sometime the
not in the blood; same thing with glucagon insulin secretion is higher than normal, the blood
o The neurotransmitters released either into the glucose level increases because the receptors are
neuromuscular junction or neuroeffector junction either decreased or gone on the target cell
also act locally; at the neuromuscular or o In upregulation, if hormone A is increased, the
neuroeffector junction, the axon terminals are receptors for itself or other hormones increases
close to the membrane of the effector cell o Example, during the trimester of pregnancy, that
 General Hormones is where the secretion of estrogen is highest and
o Site of effect is distant from site of release one important action of estrogen is to increase
o Examples: thyroid hormones, growth hormones, the production of receptors for oxytocin in the
trophic hormones from the adenohypophysis myometrium of the uterus; once the posterior
o General hormones are hormones that act on pituitary gland secreted oxytocin, it will now bind
target cell that are located far from the secretory with the receptors in the myometrium and it can
cell; they are released in the blood, it has to be stimulate uterine contraction; one action of
transported in a distant site from the secretory oxytocin is to stimulate uterine contraction but
cell oxytocin per se cannot stimulate uterine
o From the thyroid gland in the neck, thyroid contraction unless the uterus has been exposed
hormones can act on the heart, bon, muscle, GIT, to a large amount of estrogen so oxytocin can
and are all far from the thyroid gland actually stimulate contraction of an estrogen-
o Growth hormone from the anterior pituitary primed uterus
gland will act on the liver, bone, muscle, and all of o Increased estrogen → increased production of
which are far from the pituitary gland receptors → oxytocin
o TSH from anterior pituitary gland has to be o Sometimes if there are excessive amount of
transported in the thyroid gland hormone, a larger amount will bind to the
o ACTH from the anterior pituitary gland has to be receptor so the receptor is desensitized or
transported to the adrenal glands destroyed – it is down-regulated
o Example, during the post-ovulatory phase of the
VII. MECHANISM OF ACTION OF A HORMONE female monthly cycle, the predominant hormone
secreted is progesterone, although you still have
 Hormone-Receptor Interaction estrogen; one action of estrogen is to stimulate
o Receptors the innermost layer of the uterus called
 Are chemical agents endometrium to proliferate; when the
 Stereospecificity concentration of progesterone increases, it
down-regulates the receptors for estrogen so

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receptors for estrogen in the endometrium is o Phospholipid 2nd messenger system
decreased; even if you have estrogen, it cannot  A hormone will bind with a receptor on
stimulate endometrial proliferation and the outer surface of the membrane
endometrial thickening stops activating G-proteins
o Increased progesterone > increased estrogen →  Activated G proteins will now activate
decreased receptor for estrogen another enzyme system that is
phospholipase, causing breakdown of
VIII. HORMONE-RECEPTOR INTERACTION phosphoinositol bisphosphate (P1P2)
 One of the breakdown products of P1P2
 Location of Receptors
is inositol triphosphate (IP3) and the
o Cell membrane
presence of IP3 increases intracellular
 Protein, peptide, catecholamines
calcium
 Receptors for protein or polypeptide
 Calcium by itself can function as a 2nd
hormones as well as for catecholamines
messenger
are located in the cell membrane
 Other breakdown product of P1P2 is
because they cannot cross the cell
diacylglycerol (DAG), which stimulates
membrane
protein kinase C that will again cause
o Cytoplasm
phosphorylation of specific intracellular
 Steroid
proteins that will stimulate specific
 Steroid hormones are lipid soluble, they
biochemical intracellular reactions
can readily cross the cell membrane,
 Hormones that use phospholipase C
and bind with intracellular or
2nd messenger system: GnRH, GHRH,
cytoplasmic receptors
TRH, oxytocin, ADH (V1 receptor in the
o Nucleus
vascular smooth muscle),
 T3, T4
catecholamines (alpha receptor)
 Thyroid hormones bind with nuclear
angiotensin II (vascular smooth muscle)
receptors

A. MEMBRANE RECEPTORS
 Ion channel linked receptors
o H + receptor → open ion channels
o Simply known as ligand gated ion channels
o Example: Ach binds with a nicotinic receptor on
the membrane of skeletal muscle cell, the sodium
channels open allowing Na influx, depolarizing
the membrane, exciting the effector cell Fig 4. Phospholipid 2nd Messenger System.
 G-protein coupled receptor – 2nd messenger mechanism
o Adenylyl cyclase → cAMP o Calcium-Calmodulin 2nd messenger system
 H + R → activate G-protein → (+)  Present in the visceral smooth muscle
adenylyl cyclase → cAMP → (+) protein  Mechanism of action of steroid
kinase A → phosphorylate specific IC hormones: they are lipid soluble, they
proteins → (+) biochemical reaction in can readily cross the cell membrane and
the cell bind with cytoplasmic receptors and
 Receptors are located on the outer the steroid hormone complex will then
surface of the membrane while G- enter the nucleus of the cell this time,
proteins are on the inner surface of the stimulating specific DNAs that will lead
membrane to the formation of specific messenger
 Activation of G-proteins will lead to the RNAs. The messenger RNAs will move
production of intracellular ligands or out of the nucleus, stimulate the
what we call second messengers ribosomes to increase the synthesis of
 Second messengers will mediate the specific intracellular protein enzymes
action of the hormone on the target cell  T3 and T4 bind with nuclear receptors
 Hormones that use adenylyl cyclase again stimulating specific DNAs that will
cAMP system: CRH, GHIH, ACTH, FSH, cause the production of specific RNAs.
LH, TSH, HCG, PTH, calcitonin, ADH (v2 This RNAs will then move out of the
receptors in the DCT), catecholamines nucleus to stimulate the ribosomes to
(beta receptors), angiotensin II increase the synthesis of intracellular
(epithelial cells in renal tubules), enzymes
glucagon

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 Steroid hormones and thyroid
hormones can stimulate gene
transcription: it stimulates DNA and
produces mRNA so we can consider
these hormones as gene stimulators
 When we say gene stimulators, they are
steroid and thyroid hormones

o The hypothalamus secretes the growth hormone

releasing hormone that will stimulate the anterior
pituitary gland to secrete growth hormone. One
of the target cell or target organ of growth
hormone is the liver. When stimulated, it will
produce IGF I or somatomedin C. But remember
that the hypothalamus can also stimulate the
secretion of growth inhibitory hormone that will
now inhibit the anterior pituitary gland from
secreting growth hormone

o The hypothalamus secretes thyrotopin releasing

hormone that will stimulate the anterior pituitary
gland to secrete thyrotropin. Target gland now is
IX. REGULATION OF ENDOCRINE SECRETION the thyroid gland. When stimulated by TSH, it will
release T3 and T4
 Indirect Nervous Control → H-H target gland axis

o True of AP, thyroid, adrenal cortex, ovaries, testes o Not all layers of adrenal cortex is dependent on
o One mechanism that regulates endocrine ACTH. The hypothalamus will secrete
function is indirect nervous control via the corticotrophin releasing hormone that will
hypothalamic-hypophyseal target gland axis. The stimulate the anterior pituitary gland to secrete
hypothalamus secretes a releasing factor or corticotropin or ACTH. The zona glomerulosa is
releasing hormone that will stimulate specific ACTH is independent, only the zona fasciculata
cells of the anterior pituitary gland to secrete and zona reticularis are ACTH dependent.
specific trophic hormone. This trophic hormone (aldosterone secretion is not dependent on ACTH.
will act on a specific target gland to cause the The major factor that regulates the secretion of
secretion of a hormone that is why it is called aldosterone is K and RAAS). It stimulates the
hypothalamic-hypophyseal target gland adrenal cortex but only the two layers and there
o This is the mechanism that will regulate the will be secretion of cortisol and androgenic
activity of the anterior pituitary gland, thyroid, hormones.
adrenal cortex, ovaries, and testis

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Introduction to Endocrine System

o 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,
o In females, hypothalamus secretes gonadotropin TSH. If the negative feedback is exerted on the
releasing hormone that will stimulate the anterior anterior pituitary gland, it is the short loop. If it
pituitary gland to secrete FSH and LH. The target goes to the hypothalamus, it is the long loop.
gland is the ovary. The ovary will secrete estrogen
and progesterone. the cells that produce
estrogen and progesterone are different.

o Between cortisol and androgens, it is mainly the

excess in free cortisol that will have a feedback
effect because the androgens produced by the
adrenal cortex are weak so if you have excess
cortisol, negative feedback will be activated –
o In males, hypothalamus secretes gonadotropin decreased CRH, decreased ACTH.
releasing 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
sertoli cells so there will be secretion of a little
amount of estrogen and another hormone that is
inhibin. LH stimulates the interstitial cells of
Leydig that will secrete testosterone.

A. REGULATION OF HORMONE SECRETION

 Negative Feedback Control
o Excess free hormone from a target gland will o In females, increased progesterone will activate
inhibit the hypothalamus and anterior pituitary negative feedback going to the anterior pituitary
gland gland but the main effect is in LH secretion. If
there is a moderate increase in estrogen which
will happen at the beginning of the female
monthly cycle, negative feedback will be
activated but in the anterior pituitary gland,
mainly in the FSH.

o IGF I can regulate GHRH and GH by exerting a

negative feedback effect that is if it is in excess, it
inhibits the hypothalamus from secreting GHRH,
it inhibits the anterior pituitary gland from
producing growth hormone. Everything will o In males, increased testosterone activates the
decrease and it will return back to normal. If it go negative feedback – anterior pituitary gland,
beyond the normal, negative feedback will stop mainly LH. It is an increase in inhibin w=that will
so it will increase again. have a negative feedback in FSH – anterior
pituitary gland only so it is short loop

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Physiology
Introduction to Endocrine System
 Positive Feedback Control TSH, increase in T3 and T4, decreased TRH. If it is
o Excess free hormone from a target gland tertiary hyperthyroidism, increased TRH, TSH, T3
stimulates the hypothalamus and anterior and T4.
pituitary gland  Modified Negative Feedback Control
o Independent of the hypothalamus and anterior
pituitary gland
o Negative feedback is not due to excess hormone
from a target gland but to a blood metabolite
regulated by the hormone
o True for: PTH, islet of Langerhans, adrenal cortex
(aldosterone)

o Estrogen also has a positive feedback effect.

Excess free hormone from a target gland will
further stimulate the hypothalamus and anterior
pituitary gland. That is exemplified by an
excessive increase in estrogen secretion a few
hours before ovulation. So if there is excess in o Another mechanism outside of the H-H target
estrogen, positive feedback is activated to the gland axis is the modified negative feedback.
hypothalamus and anterior pituitary gland According to Berne and Levy, it is called the
resulting to further increase in GnRH, FSH, LH, and physiologic response driven feedback. This
estrogen. Excessive increase in estrogen is the mechanism can regulate hormonal activity
only one that has a positive feedback. without the involvement of hypothalamus and
o In relation to this, you have to know the three anterior pituitary gland. You have a negative
levels: hypothalamus, anterior pituitary gland, feedback effect that is not exerted by a hormone
and target gland. In endocrine system disorders, but it is exerted by a metabolite in the blood. But
there are three types: primary, secondary, and the blood concentration of that metabolite is
tertiary. If the disorder is primary, the defect is in regulated by a hormone and this type of
the target gland. If it is secondary, the problem is mechanism will regulate the activity of the
in the anterior pituitary gland. If it is tertiary, the following glands: PTH, islets of Langerhans, and
problem is in te hypothalamus. So the hormonal adrenal cortex (aldosterone).
pictures are different depending on the condition. o Parathyroid. Hypocalcemia is the major stimulus
that will cause the secretion of parathyroid
hormone. PTH acts on three target organs: bone,
intestine, and kidneys and the net effect is to
cause hypercalcemia. Hypercalcemia will inhibit
further PTH secretion. So you have a negative
feedback effect wherein hypothalamus and
anterior pituitary gland are not involved and the
negative feedback is exerted not by a hormone
but by a metabolite in the blood, in this case it is
o Example, if a patient has primary hypothyroidism,
calcium. Calcium will inhibit PTH secretion but the
the problem is in the thyroid gland so there is no
plasma calcium level is regulated by PTH.
production of T3 and t4. TRH will now increase
o Insulin and glucagon. The metabolite is blood
because there is no negative feedback. TSH will
glucose. If the blood glucose is high, insulin
also increase because there is no negative
secretion is stimulated to decrease blood glucose
feedback. Comparing it to secondary
level. If it is already low, insulin secretion is
hypothyroidism or pituitary hypothyroidism, the
inhibited.
first one to decrease is TSH. Because there is no
o In aldosterone, it is mainly hyperkalemia. If
TSH, T3 and T4 will also decrease but TRH will
potassium is increased, aldosterone is secreted to
increase since there is no negative feedback. But
remove potassium thereby decreasing it.
if it is tertiary hypothyroidism, TRH, TSH, T3 and
 Permissive Action of a Hormone
t$ are all decreased.
o PTH → Inc. Vitamin D → Inc. intestinal absorption
o In primary hyperthyroidism, you have increased
of Ca
T3 and T4 so negative feedback is activated so
o Another mechanism is permissive action of a
there is decrease in TRH and TSH. If it is secondary
hormone. This time, hormone A does not act
of pituitary hyperthyroidism, there is increase in

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Introduction to Endocrine System
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.
o 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. Vitamin D will
directly increase intestinal absorption of calcium.
Therefore, PTH indirectly increase intestinal
absorption of calcium and PTH has a permissive
action on vitamin D.
 Direct Nervous Control

 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.

REFERENCES
1. Koeppen BM, Stanton BA (eds). Berne and Levy Physiology.
6th updated ed. Philadelphia: Mosby-Elsevier, 2010.
2. Lecturer’s PPT
3. Trans of SKB Apolinario, RMT

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