The Endocrine System

Basic
Morphophysiology

EMIS ITESM

Department of Basic
Sciences
Introduction
Maintenance of homeostasis involves
coordinating activities of organs and
systems throughout the body

Endocrine system and Nervous system
are the mayor control systems




Introduction
The Endocrine System
is responsible for the
maintenance of growth,
metabolism,
development, puberty
and mood.

The endocrine and
nervous system can
work together or alone to
perform the same general
functions: to monitor and
adjust physiologic
activities

Introduction
Summary:

Major control systems:
Endocrine and nervous system work together
Function: to maintain homeostasis
Both use
specific communication methods
affect specific target organs
Their methods and effects differ.
Introduction
In general, the nervous system performs short-
term very specific responses to environmental
stimuli
- chemical messengers are neurotransmitters

The endocrine system regulates longer-term,
ongoing metabolic processes throughout the
body
- chemical messengers are hormones

Comparison of Nervous and Endocrine Systems Control
Characteristic Nervous System Endocrine System
Mediator Molecules Neurotransmitters
released locally
Hormones delivered
throughout the body
by the blood
Site of Mediator Action Close to site of
release
Usually far from site of
release
Types of target cells Muscle (smooth,
cardiac, and skeletal)
cells, gland cells,
other neurons
Cells throughout the
body
Time to onset of action Within milliseconds Seconds hours -
days
Duration of Action Typically briefer
(milliseconds)
Generally longer
(seconds to days)
Glands
A. Exocrine gland
Ducts
Lumen and
surfaces

B. Endocrine gland
Chemical
messengers
Blood stream

Endocrine System
Pituitary
The hypothalamus-pituitary unit is the most dominant
portion of the entire endocrine system.

The output of the hypothalamus-pituitary unit regulates
the function of the thyroid, adrenal and reproductive
glands and also controls somatic growth, lactation,
milk secretion and water metabolism.

The pituitary gland lies in a pocket of bone at the base
of the brain, just below the hypothalamus to which it is
connected by a stalk containing nerve fibers and blood
vessels. The pituitary is composed to two lobes--
anterior and posterior.

Pituitary
Pituitary
Anterior pituitary derived
from outpouching of
pharyngeal mucosa

Eventually pinches off
and becomes separate
from pharynx

Posterior pituitary derived
from outgrowth of
hypothalamus

Pituitary
Posterior pituitary remains connected to hypothalamus by infundibular stalk
Pituitary
The anterior,
intermediate, and
posterior lobes of
the pituitary gland
are actually three
more or less
separate endocrine
organs.

The intermediate lobe
is rudimentary in
humans. It is
separated from the
anterior lobe by the
remains of Rathke's
pouch.
Gross Anatomy - Histological Organization of the Pituitary Gland
Anterior Pituitary
All are peptide hormones
All are trophic hormones: Stimulate a target
endocrine gland to secrete increased amounts
of its own hormone (except PRL).

Anterior Pituitary
ACTH, prolactin, and growth hormone are simple polypeptides or proteins.

TSH, LH, and FSH are glycoproteins made up of two subunits ( and ).

All of the subunits of these hormones are products of a single gene and
have the same amino acid composition, although their carbohydrate
residues vary.

The subunits, which are produced by separate genes and differ in structure,
confer hormonal specificity. The subunits are remarkably
interchangeable, and hybrid molecules can be created.
Pituitary Hormones
Hypothalamic
Pituitary Axis

Pituitary Portal System
Hypothalamic-hypophyseal portal
system links anterior pituitary to
hypothalamus.

In most parts of the body, arteries
are connected with veins
through capillary plexus.
Nonetheless, in certain areas,
we can find special functional
adaptations to this system.

When capillaries connect with
vessels that, in turn, offer a
second set of capillaries
before connecting with
systemic veins, this disposition
is called a portal system.

Pituitary Portal System
Parvicellular
neurosecretory cells
secrete releasing
factors into capillaries
of the pituitary portal
system at the median
eminence which are
then transported to
the anterior pituitary
gland to regulate the
secretion of pituitary
hormones.

Pituitary Portal System
The anterior pituitary is made up
of interlacing cell cords and
an extensive network of
sinusoidal capillaries.

The endothelium of the
capillaries is fenestrated, like
that in other endocrine
organs. The cells contain
granules of stored hormone
that are extruded from the
cells by exocyrosis.

The granules presumably break
down in the peri-capillary
space, and their contents
enter the capillaries.
Posterior Pituitary
Posterior pituitary is made
up of endings of the axons
that arise from cell bodies in
the supraoptic and
paraventricular nuclei and
pass to the posterior
pituittary via the
hypothalamohypophysial
trat. Most of the supraoptic
fiber end in the posterior
lobe itself whereas some of
the paraventricular fibers
end in the median eminence.

There are also pituicytes,
stellate cells which are
modified astrocyres.

Posterior Pituitary
Hormones secreted by
posterior pituitary are
synthesized in nerve cell
bodies in hypothalamus and
secreted by axonal terminals
in posterior pituitary, and
from there into veins, which
carry them into systemic
circulation

Hormones secreted by
posterior pituitary are :

1. ADH (vasopressin)
2. Oxytocin

Both are peptide hormones.

Hypothalamic Control over Endocrine Organs
Hypothalamic Control over Endocrine Organs
Characteristics of hypothalamic releasing hormones

1. Secretion in pulses
2. Act on specific membrane receptors
3. Transduce signals via second messengers
4. Stimulate release of stored pituitary hormones
5. Stimulate synthesis of pituitary hormones
6. Stimulates hyperplasia and hypertophy of target
cells
7. Regulates its own receptor

Pituitary
Hypothalamic releasing
hormone

Effect on pituitary

Corticotropin releasing hormone
(CRH)

Stimulates ACTH secretion

Thyrotropin releasing hormone
(TRH)

Stimulates TSH and Prolactin
secretion

Growth hormone releasing
hormone (GHRH)

Stimulates GH secretion

Somatostatin

Inhibits GH (and other
hormone) secretion

Gonadotropin releasing
hormone (GnRH) a.k.a LHRH

Stimulates LH and FSH
secretion

Prolactin releasing hormone
(PRH)

Stimulates PRL secretion

Prolactin inhibiting hormone
(dopamine)

Inhibits PRL secretion

Classification of hormones
There are two classifications of hormones:
steroidal and non-steroidal
Steroidal hormones are lipid soluble and
can diffuse directly into the target cells via
the cell membrane.
Non-Steroidal hormones are synthesized
by amino acids and target cells need
receptors to diffuse into the cell.
Classification of hormones
Peptide hormones (Hydrophilic: polar)
formed from chains of amino acids
most hormones are peptide hormones
longer chains are called protein hormones
Example: growth hormone
Steroid hormones (Hydrophobic: nonpolar)
type of lipid derived from cholesterol
Example: testosterone
Biogenic amines (Hydrophobic: nonpolar)
small molecules produced by altering the structure of
a specific amino acid
Example: thyroid hormone
Water and Lipid soluble hormones

Major mechanism of hormone action


Negative feedback Loop

Positive feedback Loop
Negative Feedback Loop
Mechanism:
A stimulus starts a process
Process causes release of a hormone
Either the hormone or a product of its effects
causes the process to slow down or turn off.

Example: the regulation of the blood
glucose level in the body

Negative Feedback Loop
Positive Feedback Loop
Called positive because it accelerates the
original process
can ensure that the pathway continues to run
can speed up its activities.

Few positive feedback loops in the human
endocrine system.
Example: milk release from the mammary
glands
Positive Feedback Loop
Endocrine Glands
Thyroid gland
Largest pure endocrine gland

Internally, composed of hollow follicles
- separated by areolar CT rich in capillaries
- walls are formed of cuboidal or squamous epithelial
cells (follicular cells)
- lying within the epithelium are parafollicular (C) cells
- central lumen filled with colloid (gluelike) consisting of
thyroglobulin (protein precursor to thyroid hormone)

Amino-based TH and protein based Calcitonin

Thyroid gland
Anatomy and Histological Organization of the Thyroid Gland
Anatomy and Histological Organization of the Thyroid Gland
The Regulation of Thyroid Secretion
Thyroid function is regulated
primarily by variations in the
circulating level of TSH.

TSH secretion is increased
by TRH and inhibited in a
negative feedback fashion
by circulating free T4 and
T3.

The effect of T4 is enhanced
by production of T3 in the
cytoplasm of the pituitary
cells by the 5'-D2 they
contain.

TSH secretion is also
inhibited by stress, and in
experimental animals it is
increased by cold and
decreased by warmth.
Some of the
widespread effects
of THs in the body
are secondary to
stimulation of O2
consumption
(calorigenic action).

THs also affect
growth and
development in
mammals, help
regulate lipid
metabolism, and
increase the
absorption of
carbohydrates from
the intestine.

They also increase
the dissociation of
O2 from
hemoglobin by
increasing red cell
2,3-DPG
Parathyroid glands
Lie on the posterior surface of the thyroid gland surrounded by
CT capsules (number varies)

Contains thick branching cords composed of 2 types of endocrine
cells
- chief cells small abundant parathyroid glandular cells that
produce PTH
- Oxyphil cells and transitional cells likely immature of inactive
principal cells

Regulates calcium homeostasis: PTH increases calcium levels
and is essential to life:
1) stimulates osteoclasts to release calcium from bones
2) decreases secretion of calcium by the kidney
3) activates vit D, which stimulates uptake of Ca by the intestine
Parathyroid glands
Adrenal gland
Paired pyramidal organs on the superior surface of the
kidneys highly vascularized

3 groups of 60 small suprarenal arteries supply each gland:
- superior suprarenal arteries from the inferior
phrenic artery
- middle suprarenal arteries from the aorta;
- inferior suprarenal arteries from the renal artery

Veins
- left suprarenal vein drains into the renal vein
- right suprarenal vein drains into the inferior vena cava

Adrenal gland
Adrenal gland
Divided into 2 regions:

- Suprarenal cortex
Zona Glomerulosa mineralocorticoids
Zona Fasciculata glucocorticoids
Zona Reticularis androgens

- Suprarenal medulla
Chromaffin cells produce epinephrine and
norephinephrine
- modified ganglionic sympathetic neurons
- active in the fight, flight, and fright (fight or flight) response
- hormones stored in secretory vesicles
Adrenal gland
Adrenal gland
Both basal secretion of glucocorticoids
and the increased secretion provoked
by stress are dependent upon ACTH
from the anterior pituitary.

Angiotensin II also stimulates the
adrenal cortex, but its effect is mainly
on aldosterone secretion.

Large doses of a number of other
naturally occurring substances,
including vasopressin, serotonin, and
VIP, are capable of stimulating the
adrenal directly, but there is no
evidence that these agents play any
role in the physiologic regulation of
glucocorticoid secretion.
Mechanism of action of ACTH
When ACTH binds to its
receptor (R), adenylyl
cyclase (AC) is activated
via Gs. The resulting
increase in cAMP activates
protein kinase A, and the
kinase phosphorylates
cholesteryl ester hydrolase
(CEH), increasing its
activity.

Consequently, more free
cholesterol is formed and
converted to
pregnenolone. Note that in
the subsequent steps in
steroid biosynthesis,
products are shuttled
between the mitochondria
and the smooth
endoplasmic reticulum
(SER). Corticosterone is
also synthesized and
secreted.

Effects of Glucocorticoids
Glucocorticoids:

increase protein catabolism,
hepatic glycogenesis and
gluconeogenesis.

exert an antiinsulin action in
peripheral tissues

raise plasma lipid levels and
increase ketone body formation
but in healthy persons the
increase in insulin secretion
provoked by the rise in plasma
glucose obscures these actions
Effects of Glucocorticoids
Small amounts of glucocorticoids must be
present for a number of metabolic reactions
to occur, although the glucocorticoids do
not produce the reactions by themselves.
This effect is called their permissive action.
Permissive effects include the requirement
for glucocorticoids to be present:

for glucagon and catecholamines to exert
their calorigenic effects;

for catecholamines to exert their lipolytic
effects; and

for catecholamines to produce pressor
responses and bronchodilation.
Effects of Glucocorticoids
Glucocorticoid excess:

exert a significant mineralocorticoid
action Hypertension

leads to bone dissolution by decreasing
bone formation and increasing bone
resorption osteoporosis

accelerate the basic
electroencephalographic rhythms and
produce mental aberrations ranging
from increased appetite, insomnia, and
euphoria to frank toxic psychoses
Effects of Glucocorticoids
Pharmacological doses of corticoids:

inhibit the inflammatory response to
tissue injury
inhibit ACTH secretion to the point
that severe adrenal insufficiency
inhibit growth, decrease GH
secretion, induce PNMT, and
decrease TSH secretion
accelerate the maturation of
surfactant in the lungs (during fetal
life)
Renin Angiotensin System
Renin, an acid protease secreted by the kidneys into the
bloodstream, acts in concert with angiotensin-converting
enzyme (ACE) to form angiotensin II. It splits the decapeptide
angiotensin I from the amino terminal end of
angiotensinogen.

Angiotensinogen is synthesized in the liver. Its circulating
level is increased by glucocorticoids, thyroid hormones,
estrogens, several cytokines, and angiotensin II.

ACE is a dipeptidyl carboxypeptidase that splits off the
physiologically inactive angiotensin I, forming the
octapeptide angiotensin II

Renin Angiotensin System
Most of the converting enzyme that forms angiotensin II
in the circulation is located in endothelial cells. Much of
the conversion occurs as the blood passes through the
lungs, but conversion also occurs in many other parts of
the body.

Angiotensin II produces arteriolar constriction and a rise
in systolic and diastolic blood pressure. It is one of the
most potent vasoconstrictors known, being 4 to 8 times
as active as norepinephrine

Angiotensin II also acts directly on the adrenal cortex to
increase the secretion of aldosterone, and the renin
angiotensin system is a major regulator of aldosterone
secretion
Renin Angiotensin System
Pancreas
It is a soft,
lobulated organ
that stretches
obliquely across
the posterior
abdominal wall
in the epigastric
region.

It is situated
behind the
stomach and
extends from the
duodenum to the
spleen.
Pancreas
The pancreas is
retroperitoneal
except for a
small part of its
tail.

It consists of a
head, uncinate
process, neck,
body, and tail.
Pancreas
The pancreatic branches of splenic artery also supply the neck, body and tail of the pancreas.
The largest of those branches is called arteria pancreatica magna.

A dorsal dorsal or superior pancreatic artery has a dorsal origin in relation to the pancreas; it
is usually present, but has a great variability of origin: from the splenic artery (37%), fourth
branch of the celiac (33%), superior mesenteric (21%), and less often from the hepatic
(8%). It helps to form an inferior or transverse pancreatic artery, which supplies the lower
portion of the body

The superior
pancreaticoduodenal
artery from
gastroduodenal artery and
the inferior
pancreaticoduodenal
artery from superior
mesenteric artery
bifurcates into anterior and
posterior branches, join
each other and form
anterior and posterior
pancreaticoduodenal
arcades supplying the
pancreatic head and
uncinate process
Veins accompany the SPDA and IPDA. The body and neck of the
pancreas drain into splenic vein; the head drains into the superior
mesenteric and portal veins.

Lymph is drained via the splenic, celiac and superior mesenteric
lymph
Pancreas
Pancreas

Pancreas contains endocrine and exocrine
cells:
Exocrine acinar cells, form most of the gland
- secrete a powerful, digestive fluid digestive juice
with enzymes into the duodenum; its duct joins the
common bile duct
Endocrine cells are contained in spherical
bodies
- pancreatic islets or islets of Langerhans
- about 1 million scattered among the exocrine cells

Pancreas
Each islet contains 4 major cells

Alpha cells glucagon
Beta cells insulin
Delta cells somatostatin (growth-hormone
inhibiting hormone)
F cells pancreatic polypeptide (PP)

Hormones of Pancreas
Pancreas
Glucagon raises blood
glucose levels.

Insulin lowers blood
glucose levels.

Somatostatin inhibits both
glocagon and insulin
release.

Pancreatic polypeptide
inhibits somatostatin
secretion, gallbladder
contraction and secretion
of digestive enzymes by
the pancreas.

Glucagon
Hypoglycemia
stimulates
release of
glucagon

Glucagon
causes
hepatocytes to
convert
glycogen to
glucose
(glycogenolysis)

Hyperglycemia
inhibit release
of glucagon

Insulin
Insulin allows glucose
to diffuse into cells,
increases amino acid
uptake by cells, and
increaes fatty acid
uptake by cells.

This facilitates
glucose conversion
into glycogen
(glycogenesis),
synthesis of proteins,
and synthesis of fatty
acids (lipogenesis).

Insulin: Mechanism of Action
Binding of insulin triggers the tyrosine
kinase activity of the subunits,
producing autophosphorylation of the
subunits on tyrosine residues. The
autophosphorylation, which is
necessary for insulin to exert its
biologic effects, triggers
phosphorylation of some cytoplasmic
proteins and dephosphorylation of
others, mostly on serine and threonine
residues.

Four related insulin receptor substrate
(IRS) proteins in cells have been
described (IRS - I to IV). IRS-1 has
received the most attention, but
pathways in addition to IRS-l play
important roles in the actions of
insulin.
Exposure to increased amounts of
insulin leads to down regulation.
Insulin: Mechanism of Action
Effects of Insulin


The physiologic effects of
insulin are far-reaching
and complex.
Effects of Insulin
Rapid (seconds)

Increased transport of
glucose, AA and K into
insulin-sensitive cells

Delayed (hours)

Increase in mRNA for
lipogenic and other
enzimes

Intermediate (minutes)

Stimulation of protein
synthesis
Inhibition of protein
degradation
Activation of glycolytic
enzimes and glycogen
synthase
Inhibition of phosphorilase
and gluconeogenic
enzimes

Effects of Insulin
Glucose enters cells by facilitated diffusion or, in the intestine
and kidneys, by secondary active transport with Na+.

In muscle, fat and some other tissues, insulin facilitates glucose
entry into cells by increasing the number of glucose transporters in
the cell membranes.

They differ from and have no homology with the sodium-dependent
glucose transporters, SGLT 1 and SGLT 2, responsible for the
secondary active transport of glucose out of the intestine and renal
tubules, although the SGLTs also have 12 transmembrane domains.

Seven different glucose transporters have been characterized. They
contain 492-524 amino acid residues, and their affinity for glucose
varies. Each transporter appears to have evolved for special tasks.
Effects of Insulin
Effects of Insulin
GLUT 4 is the transporter in
muscle and adipose tissue
that is stimulated by insulin. A
pool of GLUT 4 molecules is
maintained in vesicles in the
cytoplasm of insulin-sensitive
cells.

When the insulin receptors of
these cells are activated, the
vesicles move rapidly to the
cell membrane and fuse with
it, inserting the transporters
into the cell membrane.

When insulin action ceases,
the transporter-containing
patches of membrane are
endocytosed, and the
vesicles are ready for the next
exposure to insulin.


Activation of the insulin receptor brings about the
movement of the vesicles to the cell membrane by
activating phosphoinositol-3 kinase.

Insulin also increases the entry of glucose into liver
cells, but it does not exert this effect by increasing
the number of GLUT 4 transporters. Instead, it
induces glucokinase, and this increases the
phosphorylation of glucose, so that the intracellular
free glucose concentration stays low,
facilitating the entry of glucose into the cell.
Pancreas


Interactions between
Glucagon and Insulin
Starvation
Gonads
Ovaries (female gonads).
Produce steroid hormones.
Estrogens.
Progesterone.
Produce inhibin.
Produce relaxin.

Testes (male gonads).
Produce testosterone (an androgen).
Produce inhibin.


Gonads
Testes:
- Interstitial cells produce androgens (testosterone)
promotes production of functional sperm, maintains
secretory glands, influences 2
nd
sexual characteristics,
and stimulates muscle growth
- Nurse cells (or sustentabular cells) secrete inhibin

Ovaries
- Follicular cells produce estrogens and inhibin
- Corpus luteum releases progestins and relaxin
Gonads
Female sex hormones
Estrogen and progesterone along with FSH and LH (from the
anterior pituitary), regulate the menstrual cycle, maintain
pregnancy, and prepare the mammary glands for lactation.
Maintain the feminine secondary sex characteristics (larger
breasts and hips).
Inhibin inhibits secretion of FSH.
Relaxin increases the flexibility of the pubic symphisis during
pregnancy and helps dilate the cervix during labor and delivery.

Male sex hormones
Testosterone regulates the production of sperm. maintains
secretory glands, and stimulates muscle growth.
Stimulates the production of male secondary sex
characteristics (beard growth and deepening of the voice).

Pineal
A small
endocrine
gland
attached
to the
roof of
the third
ventricle
of the
brain.

Pineal
Contains neurons, glial cells, and special secretory
cells called pinealocytes

Secretes melatonin

Production rates rises at night (darkness) and
declines during the day

Melatonin contributes to the bodys biological clock.

Melatonin slows the maturation of sperm, oocytes,
and reproductive organs
Clinical Note - Endocrine Abnormalities
Clinical
Implications of
Endocrine
System
Pour tre subversif, il faut tre subjectif
(Frdric Beigbeder)
Adrin