Endocrine System

 System of glands(ductless) that release extracellular signaling molecules, known as

hormones to directly into the blood stream
 Functions
o Metabolism( The endocrine system regulates the rate of metabolism and influences the
maturation of tissues such as of the nervous system)
 E.g Thyroid hormones
o Ion Regulation( The endocrine system regulate blood ph as well as the Na, K and Ca
concentrations in the blood)
o Water Regulation( regulates water balance in controlling the solute concentration of the
blood)
 E.g Antidiuretic Hormone
o Immune System Regulation
 E.g Tyrosine
o Heart rate and Blood pressure regulation
 E.g. Epinephrine and Norepinephrine
o Control of Blood Glucose and other nutrients
 E.g. Insulin and Glucagon
 o Control of Reproductive functions
 E.g. Testosterone and Estrogen
o Uterine Contractions and milk release
 E.g. Oxytocin

ANATOMY
 Organs of the Endocrine System
o Hypothalamus
 Part of the diencephalon located below the thalamus and is connected to the
pituitary gland
 It secretes Releasing Hormones for the pituitary gland
 Secretes Oxtocin that is stored in the Posterior pituitary gland
 Secretes Anti-Diuretic Hormone or Vasopressin that is also in the posterior pituitary
gland.
o Pituitary Gland
 The master gland
 Located below the hypothalamus at the base of the brain
 Divided into two parts
 Anterior Pituitary gland
o Adenohypophisis
o Release and synthezise hormones
 Growth hormone (GH)
 Stimulates growth of bone and muscle, promotes protein
synthesis and fat metabolism, decreases carbohydrate
metabolism
 Adrenocorticotropic hormone (ACTH)
 Stimulates synthesis and secretion of adrenal cortical hormones
 Thyroid-stimulating hormone (TSH)
 Stimulates synthesis and secretion of thyroid hormones
 Follicle-stimulating hormone (FSH)
 Female: stimulates growth of ovarian follicle, ovulation
 Male: stimulates sperm production
 Luteinizing hormone (LH)
 Female: stimulates development of corpus luteum, release of
oocyte, production of estrogen and progesterone
 Male: stimulates secretion of testosterone, development of
interstitial tissue of testes
 PosteriorPituitary Gland
o Neurohyphophisis
o Does not produce but stores and release
 Antidiuretic hormone
 Increase water reeabsorption by kidney
 Oxytocin
 Stimulates Uterine contraction and milk ejection
o Thyroid gland
 Located in the anterior neck lateral to the trachea
 Produces thyroid hormones by the thyroid follicles
 primary function of the thyroid hormone is to control the cellular metabolic
activity.
  The secretion is controlled by thyroid-stimulating hormone (TSH, or
thyrotropin) from the anterior pituitary gland.
 Regulation
o Nuerotransmitters  HypothalamusThyrotropin-releasing
hormone(TRH)Pituitary GlandThyroid Stimulating
HormoneThyroidT3&T4 Target organs
 These hormones accelerate metabolic processes by increasing the level of
specific enzymes that contribute to oxygen consumption and altering the
responsiveness of tissues to other hormones.
 Triidothyronine( T3)
o T3 is about five times as potent as T4 and has a more rapid metabolic
action.
o Cellular Metabolism
 Thyroxine (T4)
o Metabolism(Catbolic phase)
o T4, a relatively weak hormone, maintains body metabolism in a steady
state
 Thryrocalcitonin
o Calcium Balance.
o Parathyroid gland
 Located at the back of the thyroid gland (four in number)
 Secretes Parathyroid hormone
 protein hormone from the parathyroid glands that regulates calcium and
phosphorus metabolism.
 Increased secretion of parathormone results in increased
calcium absorption from the kidney, intestine, and bones,
thereby raising the blood calcium level
o Adrenal Glands
 Two small glands lying in the retroperitoneal region
 Adrenal Medulla
o The adrenal medulla functions as part of the autonomic nervous
system.
o Stimulation of preganglionic sympathetic nerve fibers,which travel
directly to the cells of the adrenal medulla, causes release of the
catecholamine hormones epinephrine and norepinephrine.
 Adrenal Cortex
o promotes organic metabolism, regulates sodium and potassium,
response to stress, preadolescent growth spurt
 Glucocorticoids
 Gluconeogenesis
 Regulates blood sugar by conserving glucose and cortisone
 Mineralocorticoids
 Aldosterone, corticosterone
 Regulates electrolyte balance by Na retention and K excretion
 Androgens and Estrogens
 Secondary sex characteristics
o Pancreas
 This retroperitoneal organ has both endocrine and exocrine functions
 The endocrine function resides in the Islets of Langerhans
 The islets have three types of cells- alpha, beta and delta cells
  The Alpha Cells Secrete Glucagon
 The Beta Cells Secrete Insulin
 The Delta Cells Secrete Somatostatin
o Gonads
 Responsible for secondary sex characteristics and reproductive function
 ovaries,
 estrogen, progesterone, inhibin - decreases secretion of follicle-stimulating
hormone (FSH)
 testes
 testosterone
 Location:
 two ovaries are situated in the lower abdomen on each side of the uterus.
 The testes are the pair of male sex organs that form within the abdomen but
descend into the scrotum
 Endocrine Signaling
o Autocrine- Target same cell or other cell (e.g Adrenal Glands)
o Paracrine- Target cells is near the signal-releasing cell ( e.g.Testosterone in the testes)
o Juxtacrine-transmitted via oligosaccharide, lipid, or protein components of a cell
membrane, and may affect either the emitting cell or the immediately-adjacent cells.
 Classification of Hormones
o Amino Acids- Binds to membrane-bond receptor sites on the target cells of organs.
 E.g. oxytocin & vasopressin by the adrenal medulla, Epinephrine, Thyroxine
o Protein Hormones-Must be injected because they cannot diffuse across membrane.
 E.g Insulin and Growth Hormones
o Steroid Hormones- Which are soluble in lipids & can diffuse across lining of the stomach
and intestines and get to the circulatory system.
 E.g Adrenal Cortex(Cortisol), Gonads( Testosterone & Estrogen)

Source Hormone Type Function

Hypothalamus Antidiuretic Protein Promotes reabsorption of water in
via posterior Hormone (ADH) kidneys and sweat glands; constricts
pituitary arterioles
Oxytocin Protein In females, stimulates contraction of
uterine muscles during childbirth, milk
ejection, and maternal behaviours
In males, causes sperm ejection
Anterior Thyroid-Stimulating Glycoprotein Stimulates thyroid to release thyroxine
Pituitary Hormone (TSH)
Growth Hormone Protein Stimulates growth, protein synthesis,
(somatotropin) and fat metabolism; inhibits sugar
metabolism
Adrenocorticotropic Protein Stimulates adrenal cortex to release
Hormone (ACTH) hormones, especially glucocorticoids
Thyroid Thryoxine (T4) Modified Increases metabolic rate of most body
amino acid cells, increases body temperature;
regulates growth and development
Calcitonin Protein Inhibits release of calcium from bones
 Triiodothyonine (T3) Modified Increases metabolism; regulates
amino acid growth
Parathyroid Parathormone Protein Stimulates release of calcium form
bone; promotes absorption of calcium
by intestines; promotes reabsorption of
calcium from kidneys
Adrenal Adrenalin and Modified Increase lvels of sugar and fatty acids
Medulla noradrenalin amino acids in blood; increase metabolic rate;
increase rate and force of contractions
of the heart; constricts some blood
vessels
Adrenal Glucocorticoids Steroid Increase blood sugary; regulate sugar,
Cortex (cortisol) lipid, and fat metabolism; anti-
flammatory effects
Aldosterone Steroid Increases reabsorption of salt in kidney
Testosterone Steroid Causes masculinisation of body
features, growth
Pancreas Insulin Protein Decreases blood glucose levels by
increasing uptake of glucose into cells
and converting glucose to glycogen,
especially in liver; regulates fat
metabolism
Glucagon Protein Converts glycogen to glucose, thereby
raising blood glucose level

PHYSIOLOGY
Hormones = Chemicals secreted by a cell or group of cells into the blood, that act on distant
target(s) and are effective at very low concentrations.
Hormones play a major role in growth and development, metabolism, regulation of
the internal environment (temperature, water balance, and ions), biological clock,
contraction of cardiac and smooth muscle, some immune functions and reproduction.
Hormones act on target cells three different ways:
1. By controlling the rates of enzymatic reactions (modulate activity, change amount
of enzyme).
2. By controlling the transport of ion molecules across the membrane (open/close
channels, modulate transporters).
3. By controlling gene expression and synthesis of proteins (“genomic effects”).

 Cellular mechanism of action = Biochemical response(s) initiated by hormone at target

cell(s).
 Half-life = Amount of time required to reduce a hormone concentration in half
 Hormones must be transported via blood to distant targets.
Hormone Action Depends on Specific Receptors as Well as Hormone Properties.

Hormones only affect target cells with specific membrane proteins called receptors!!!!!!!!!
Distinction between nervous and
endocrine system is no longer
clear-cut

1. Exocrine glands
 secrete products into
ducts which empty into
body cavities or body surface
  sweat, oil, mucous, & digestive glands
2. Endocrine glands
 secrete products (hormones) into bloodstream
 pituitary, thyroid, parathyroid, adrenal, pineal
 other organs secrete hormones as a 2nd function
 hypothalamus, thymus, pancreas, ovaries, testes, kidneys, stomach, liver, small
intestine, skin, heart & placenta
Hormones Have Been Known Since Ancient Times
“Goiter was endemic high in the Andes due to lack of iodine in the diet. People living near the
coast where they could eat seafood rich in iodine did not exhibit much goiter. In ancient China,
low-iodine goiter was treated by drinking a powder of burnt seaweed dissolved in wine, an
effective remedy because marine plants and animals contain substantial amounts of iodine”.
Link between castration and endocrine structure/function
1. Link between testies and male sexuality: Castration of animals and men in both Eastern and
Western culture was common practice decreased sex drive and male infertility.
A. A. Berthold’s experiments became a template for endocrine research: “ In 1849 Berthold
removed testies from roosters smaller combs & less aggressive. If testies were placed back into
the bird normal behaviour and comb development. Since the re-implanted testies were not
connected to nerves, the glands must be secreting something into the blood that affected the
entire body”.
The Classification of Hormones
Hormones are categorized into three main chemical classes:
 peptide/protein hormones (composed of amino acids)
 steroid hormones (derived from cholesterol)
 amino-acid hormones (modifications of single amino acids, either tryptophan
or tyrosine)
Classic hormones: are hormones secreted by an endocrine gland or cell, may be a peptide,
steroid, or amine in nature.
Neurosecretory hormones: are hormones secreted by nerve cells and are either peptide or
amines
Most Hormones are Peptides or Proteins
Peptide/protein hormones range from small peptides of only three amino acids to larger proteins
and glycoproteins. Despite their size among hormones in this group they are usually called
peptides for simplistic sake.
You can remember which hormones fall into this category by exclusion: if a hormone is not a
steroid hormone and not an amino acid derivative, then it must be a peptide or protein.
Peptide Hormone Synthesis, Storage, and Release
Synthesis and packaging of peptide hormones into membrane bound vesicles is similar of that
to other proteins.
1 Initial peptide comes off ribosome is a large inactive protein known as a
preprohormone
(Preprohormones contain one or more copies of peptide hormones)
 2 As the inactive preprohormone moves through the endoplasmic reticulum and golgi
complex, the signal sequence is removed, creating a smaller, still-inactive molecule
called a prohormone.
3 In the golgi complex, the prohormone is packaged into a secretory vesicles along with
proteolytic enzymes that chop the prohormone into active hormone and other fragments.
This process is called pot-translation modification
4 The secretory vesicles containing peptides are stored in the cytoplasm of the endocrine
cell until the cell receives a signal for secretion.
5 The vesicles are transported out of the cell via calcium-dependent exocytosis

Post-translational Modification of Prohormone

There are many possible scenarios for post-translational processing
1. Multiple copies of the hormone
a) PreProTRH (thyrotropin-releasing hormone) has 6 copies of the 3-amino acid hormone TRH.

Prohormone’s such as pro-opiomelanocortin, the prohormone for ATCH may contain several
peptide sequences with biological activity
Cellular Mechanism of Action of Peptide Hormones
A. Peptides are lipophobic (hate lipids), so they have membrane receptors.
B. Signal transduction sets off cellular response.
C. Can act on existing cell products, so have a quick response time.

Many peptides work through cAMP second messenger systems

Steroid Hormones are Derived from Cholesterol

Steroid hormones have similar chemical structures because they are derived from cholesterol.
Steroid hormones are made in only a few organs. Three types of steroid hormones are made in
the adrenal cortex, the outer portion of the adrenal glands. The gonads produce sex steroids. In
pregnant women, the placenta is also a source of steroid hormone.

Cellular Mechanism of Action of Steroid Hormones

The best studied steroid hormones receptors are found within cells, either in the cytoplasm or
nucleus. The ultimate destination of steroid receptor-hormone complexes is the nucleus, where
the complex acts as transcription factor, binding to DNA and activating or depressing one or
more genes.
Activated genes create new mRNA that directs the synthesis of new proteins. Any hormone that
alters gene activity is said to have a genomic effect on the target cell.
When steroid hormones activate genes to direct the production of new proteins, there is usually
a lag time between hormone receptor binding and the first measurable biological effects. This
lag can be up to 90 min.
Estrogens and aldosterone, have cell membrane receptors linked to signal transduction
pathways, just as peptide hormones do. These receptors enable those steroid hormones to
initiate rapid nongenomic responses in addition to slower genomic effects.
1. Intracellular receptors in cytoplasm or nucleus.
2. Hormone-receptor complex acts as a transcription factor directing synthesis of gene products.
3. Lag time of action due to synthesis of new proteins
4. Can have surface receptors/signal transduction (e.g., estrogen, aldosterone) with more rapid
effects
Some Hormones are derived from Single Amino Acids
A. Melatonin (tryptophan)
B. Catacholamines (tyrosine): Behave like peptide hormones.
C. Thyroid hormones (tyrosine): Synthesized more like peptide hormones, but behave like
steroid hormones once released from the thyroid cell.
The thyroid hormones are unique among hormones because iodine is a key part of each
thyroid molecule. Like peptide hormones, thyroid hormones are made in advance and stored in
an inactive form waiting release. Once converted to the active form, the thyroid hormones
behave as if they are steroid hormones. Thyroid hormones are lipophilic so they diffuse freely
across cell membranes and are carried bound to proteins in the blood. Only free (unbound)
hormones diffuse across the target cell membrane to combine with a nuclear receptor. And like
the steroid-receptor complex, the thyroid-receptor complex initiates transcription, translation and
protein synthesis.
Negative Feedback Turns Off Hormone Reflexes

A. Negative feedback signal turns off response.

1. Ex. increased blood glucose levels reflex response decreased blood glucose turns off the
reflex.
B. Hormones act as negative feedback signals in complex reflexes
C. Hormones usually act as negative feedback
signals only when trophic hormones are
involved

The Pituitary Gland is Actually Two Fused Glands

Neurohormones of the Posterior Pituitary

A. Stores and releases oxytocin and vasopressin (ant diuretic hormone).

B. Peptides made in hypothalamus stored in secretory vesicles transported down an axon to
posterior pituitary for release
 Does not synthesize hormones
 Consists of axon terminals of hypothalamic neurons
 Neurons release two neurotransmitters that enter capillaries
Oxytocin
Two target tissues both involved in neuroendocrine reflexes
 During delivery - baby’s head stretches cervix hormone release enhances uterine
muscle contraction and baby & placenta are delivered
 After delivery - suckling & hearing baby’s cry stimulates milk ejection, hormone causes
muscle contraction & milk ejection
 Ant diuretic Hormone (ADH)
Also known as vasopressin which functions include:
1 decrease urine production
2 decrease sweating
3 increase BP

Complex Endocrine Pathways Include Two or More Hormones

Hormones of the Anterior Pituitary

A. Six hormones: prolactin, growth hormone (GH), the gonadotrophins (follicle-stimulated
hormone, or FSH and leutinizing hormone, or LH), adrenocorticotrophic hormone (ATCH or
corticotropin), thyroid stimulating hormone (TSH or thyrotropin)
B. Of these, only prolactin is not trophic
C. Feedback in hypothalamic-pituitary system
1. Concentration change of one hormone concentration change for other hormones in axis.
2. Long-loop negative feedback: Hormone from last integrating center affects secretion of
trophic hormones from hypothalamus or pituitary
3. Short-loop negative feedback: Hormones of pituitary affect secretion of trophic hypothalamic
hormone.

Human Growth Hormone

• Produced by somatotrophs
• Within target cells increases synthesis of insulin-like growth factors that act locally or
enter bloodstream
1 common target cells are liver, skeletal muscle, cartilage and bone
2 increases cell growth & cell division by increasing their uptake of amino acids &
synthesis of proteins
3 stimulate lipolysis in adipose so fatty acids used for ATP
4 retard use of glucose for ATP production so blood glucose levels remain high enough to
supply brain
Regulation of HGH
• Low blood sugar stimulates release of GHRH from hypothalamus
– anterior pituitary releases more hGH, more glycogen broken down into glucose
by liver cells
• High blood sugar stimulates release of GHIH from hypothalamus
– less hGH from anterior pituitary, glycogen does not breakdown into glucose
Thyroid Stimulating Hormone (TSH)
• Hypothalamus regulates thyrotroph cells
• Thyrotroph cells produce TSH
• TSH stimulates the synthesis & secretion of T3 and T4
• Metabolic rate stimulated

Follicle Stimulating Hormone (FSH)

• Releasing hormone from hypothalamus controls gonadotrophs
• Gonadotrophs release follicle stimulating hormone
• FSH functions
– initiates the formation of follicles within the ovary
– stimulates follicle cells to secrete estrogen
– stimulates sperm production in testes
Luteinizing Hormone (LH)
• Releasing hormones from hypothalamus stimulate gonadotrophs
• Gonadotrophs produce LH
• In females, LH stimulates
– secretion of estrogen
– ovulation of 2nd oocyte from ovary
– formation of corpus luteum
– secretion of progesterone
• In males, stimulates interstitial cells to secrete testosterone

Prolactin (PRL)
• Hypothalamus regulates lactotroph cells
• Lactotrophs produce prolactin
• Under right conditions, prolactin causes milk production
• Suckling reduces levels of hypothalamic inhibition and prolactin levels rise along with
milk production
• Nursing ceases & milk production slows

Adrenocorticotrophic Hormone
• Hypothalamus releasing hormones stimulate corticotrophs
• Corticotrophs secrete ACTH & MSH
 • ACTH stimulates cells of the adrenal cortex that produce glucocorticoids

Melanocyte-Stimulating Hormone
• Secreted by corticotroph cells
• Releasing hormone from hypothalamus increases its release From the anterior pituitary
• Function not certain in humans (increase skin pigmentation in frogs )

A. Synergism: Combined action of hormones A+B > summed action of A alone + B alone
B. Ex: epinephrine and glucagon
Antagonism
A. Antagonism: Hormone B diminishes the effect of hormone A.
B. Ex: growth hormone or glucagon, both of which increases blood glucose, may be considered
antagonistic to insulin

Permissiveness
A. Permissiveness: Hormone A will not exert full effect without presence of hormone B
B. Ex. throid hormone and growth hormone
Antagonism:
A. Antagonism: Hormone B diminishes the effect of hormone A
B. Ex: growth hormone or glucagon, both of which increase blood glucose, may be considered
antagonistic to insulin
The concept of antagonism is used several ways. In pharmacological antagonism, a drug is
considered antagonistic if it binds to and inactivates a receptor for another drug by acting as
either a competitive or allosteric competitor. For example, mifepristone, better known as RU
486, is an artificial steroid that binds to the progesterone receptor and prevents endogenous
progesterone from binding.
In physiologic antagonism, two molecules need only have opposing physiological effects to
be considered antagonists. Thus, glucagon and insulin are antagonistic because of their
opposing effects on blood glucose. Growth factors fall into two sets of antagonistic molecules,
those that stimulate growth and those that inhibit it. The opposing effects of growth factors may
occur at the levels of the signal transduction pathway, with one factor increasing cAMP levels
while the antagonistic factor decreases it.