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THE ENDOCRINE SYSTEM

Endocrine Glands
• Are ductless glands
• Consists of cells that produce internal secretions called hormones
Hormones are
• Chemical messengers
• Enter directly into the bloodstream
• Regulate and integrate body functions
• Play role in body’s metabolism and growth
• Cells of endocrine glands secrete hormones into the extracellular fluid
• Hormones enter the capillaries through diffusion and secrete directly into the
bloodstream (plasma part of the blood)
• Through blood circulation, these hormones can be distributed all over our body.
Functions of the Endocrine System
 Controls the processes involved in movement and physiological equilibrium
 Includes all tissues or glands that secrete hormones into the blood
 Secretion of most hormones is regulated by a negative feedback system
 The number of receptors for a specific hormone can be altered to meet the body’s
demand

Figure 1: Human Endocrine system


Endocrine versus Nervous system
• Nervous system performs short term crisis management
• Endocrine system regulates long term ongoing metabolic
• Endocrine communication is carried out by endocrine cells releasing hormones,
• Alter metabolic activities of tissues and organs
• Target cells
• Paracrine communication involves chemical messengers between cells within one
tissue.
• Autocrine cells act on the same cell that produced them.

Figure 2:Mechanism of paracrine and autocrine cells

Chemical Classification of Hormones

Lipid soluble hormones Water soluble hormones

1. Steroid Hormones: Amine hormones –NE, Epinephrine and


2. Thyroid hormones: T3&T4 dopamine.
3. The gas nitric oxide: NO Peptide hormones-ADH ,Oxytocin.
 Lipid soluble Protein hormones including : growth
 Diffuse through cell hormone and insulin
membranes The eicosanoid hormones: are derived
 Endocrine organs from arachidonic acid . the two eicosanoids
 Adrenal cortex are prostaglandins and leukotrines.
 Ovaries
 Testes
 Placenta

Mechanisms of hormone action


1. Receptors for catecholamine, peptide hormones, eicosanoids are in the cell
membranes of target cells
• React with specific receptors outside the cell
• This triggers an enzyme reaction with lead to the formation of a second
messenger cyclic adenine monophosphate (cAMP).
• cAMP can produce specific intracellular functions:
• Activates cell enzymes
• Change in membrane permeability
• Promote protein synthesis
• Change in cell metabolism
• Stimulation of cell secretions

2. Thyroid and steroid hormones cross the membrane and bind to receptors in
the cytoplasm or nucleus:
• Pass through the cell membrane.
• Binds to specific receptors
• Then enters the nucleus to bind with the cells DNA which then activates certain
genes (Direct gene activation).
• mRNA is synthesized in the nucleus and enters the cytoplasm and promotes
protein synthesis for:
• Enzymes as catalysts
• Tissue growth and repair
• Regulate enzyme function

Negative Feedback
 Negative feedback is the primary mechanism through which your endocrine
system maintains homeostasis
 Secretion of a specific hormone s turned on or off by specific physiological
changes (similar to a thermostat)
 EXAMPLE: plasma glucose levels and insulin response
Number of Receptors
 Down-regulation: is the decrease of hormone receptors which decreases the
sensitivity to that hormone
 Up-regulation: is the increase in the number of receptors which causes the cell to
be more sensitive to a particular hormone
Pituitary Gland (Master of endocrine gland)

The pituitary gland is a pea shaped structure that measures 1-1.5cm (0.5 inch) in
diameter and lies in the hypophyseal fossa of the sella turica of the sphenoid bone. It
attaches to the hypothalamus by a stalk, the infundibulumand has two functionally
separate lobes.
The anterior pituitary (anterior lobe ), also called the adenohyphophysis, accounts for
about 75% of total weight of the gland.
The anterior pituitary consist of two parts in an adult :
The pars distalis is the larger portion.
The pars tuberalis forms sheath around the infundibulum.
The posterior pituitary (posterior lobe ), also called the neurohypophysis consist of
two parts: the pars nervosa-the larger bulbar portion , and the infundibulum.
Pars intermedia atrophies during human fetal development and ceases to exist as a
separate lobe in adult.
Anterior Pituitary
The anterior pituitary or adenohypophysis secrete hormone that regulate a wide range of
bodily activities, from growth to reproduction. Release of anterior pituitary hormone is
stimulated by releasing hormone and suppressed by inhibiting hormone from
hypothalamus.
Figure 3: The Anatomy and Orientation of the Pituitary Gland
The Hypophyseal Portal System

Hypothalamic hormone reach the anterior pituitary


through a portal system .Usually , blood passes from the
heart through an artery to a capillary to a vein and back
to the heart. In a portal system, blood flows from one
capillary network into a portal vein, and then into a
secondary capillary network without passing through
heart. The name of portal system indicates location of
the second capillary network. Superior hypophyseal
arteries, branches of internal ceratoid arteries, bring
blood into the hypothalamus. At the junction of the
median eminence of the hypothalamus and the
infundibulum, these arteries divided into a capillary
Figure 4: The Hypophyseal Portal System network called the primary plexus of the hypophyseal
portal system
Near the median eminence and above optic chiasm are
Types of anterior pituitary cells: Five types clusters of specialized neurons, called neurosecretory
of anterior pituitary cells- somatotrophs, cells. of the hypothalamus
thyrotrophs, gonadotrophs, lactotrophs and corticotrophs-secrete seven hormones

Anterior pituitary cells Releasing hormone Inhibiting hormone


(Hormone)
Somatotrophs Human growth hormone or Growth hormone –inhibiting
somatotropin- growth hormone , hormone also known as
also known as somatocrinin somatostatin.

Thyrotropin releasing hormone


Thyrotroph(TSH) Growth hormone –inhibiting
Gonadotrophic releasing hormone
hormone(GnRH)
Gonadotrophs (FSH/LH) ------
Prolactin releasing hormone
(PRH) .TRH Prolactin inhibiting hormone
Lactotrophs (PRL) (PIH), which is dopamine.

Corticotroph (ACTH) Corticotropin releasing


hormone(CRH) ---------

Corticotroph (MSH) Corticotropin releasing


hormone(CRH) Dopamine
Figure 5: Feedback control of Endocrine Secretion

Thyroid stimulating hormone (TSH)


• Triggers the release of thyroid hormones
• Thyrotropin releasing hormone promotes the release of TSH
Adrenocorticotropic hormone (ACTH)
• Stimulates the release of glucocorticoids by the adrenal gland
• Corticotrophin releasing hormone causes the secretion of ACTH
Follicle stimulating hormone (FSH)
Stimulates follicle development and estrogen secretion in females and sperm
production in males.
Leutinizing hormone (LH)
Causes ovulation and progestin production in females and androgen
production in males.
Gonadotropin releasing hormone (GNRH) promotes the secretion of FSH and LH.

Prolactin (PH)
• Stimulates the development of mammary glands and milk production
Growth hormone (hGH or somatotropin)
• Stimulates cell growth and replication through release of somatomedins or
IGF(Insulin like Growth factor)
• Growth-hormone releasing hormone
(GH-RH)
• Growth-hormone inhibiting hormone
(GH-IH)
• May be secreted by the pars intermedia during fetal development, early
childhood, pregnancy or certain diseases
• Stimulates melanocytes to produce melanin

Melanocyte stimulating hormone (MSH)


• May be secreted by the pars intermedia during fetal development, early
childhood, pregnancy or certain diseases
• Stimulates melanocytes to produce melanin
The posterior lobe of the pituitary gland (neurohypophysis)
• Contains axons of hypothalamic nerves
• Neurons of the supraoptic nucleus manufacture antidiuretic hormone (ADH)
• Decreases the amount of water lost at the kidneys
• Elevates blood pressure
• Neurons of the paraventricular nucleus manufacture oxytocin
• Stimulates contractile cells in mammary glands
• Stimulates smooth muscle cells in uterus
ADH: is a substance that decreases urine production. ADH causes the kidney to return
more water to the blood, thus decreasing urine volume. In the absence of ADH, urine
output increases more than tenfold, from the normal 1-2 lit to about 20 liters a day. ADH
also decreases the water lost through sweating and causes constriction of arterioles,
which increases blood pressure. This hormone’s other name, vasopressin, reflects these
effect on blood pressure.

Oxytocin:
During and after delivery of baby, oxytocin affects two target tissues: the mother uterus
and breasts. During delivery oxytocin enhance contraction of smooth muscle cell in the
wall of the uterus ; after delivery , it stimulates milk ejection from the mammary gland in
response to mechanical stimulus provided by suckling infant .
Thyroid gland
The butterfly – shaped thyroid gland is located just inferior to the larynx.
It is composed of right and left lateral lobes, one on either side of trachea, that are
connected by an isthmus anterior to the trachea.

Figure 6 : Thyroid Gland

A small, pyramidal-shaped lobe sometimes extends upward from the isthmus.


The normal mass of the thyroid is about 30 g.
It is highly vascularised and receives 80-120 ml of blood per min.
Microscopic spherical sacs called thyroid follicles makes up the most of thyroid gland.
The wall of each follicle consists primarily of cells called follicular cells, most of which
extend to the lumen of the follicle.
A basement membrane surrounds each follicle.
When the follicular cells are inactive, their shape is low cuboidal to squamous, but under
the influence of TSH they become active in secretion and ranges from cuboidal to low
columnar in shape.
The follicular cells produce two hormones: thyroxin (tetraiodothyronin) or T4 because
it contains four atoms of iodine, and triiodothyronin or T3, which contains three atoms
of iodine.T3 and T4 are also known as thyroid hormones.
A few cells called parafollicular cells or C cells lies between follicles.
They produce the hormone calcitonin, which helps regulate calcium homeostasis.
Figure 7: Thyroid follicle
Action of thyroid hormone:
Because most body cells have receptors for thyroid hormone T3 and T4.
1. Thyroid hormone increases BMR (Basal Metabolic Rate), the rate of oxygen
consumption under standard or basal condition (awake, at rest and fasting).
2. It stimulate synthesis of additional Na+-K+ pump, which uses large amount of
ATP to continually eject Na+ from cytosol into ECF and K+ ion from ECF to
cytosol . As cell produces and uses more ATP, more heat is given off, and body
temp rises. The phenomenon is called calorigenic effect.
3. In the regulation of metabolism thyroid hormone stimulate protein synthesis and
increase the use of glucose and fatty acids for ATP production,
4. The thyroid hormone enhances some action catecholamine because they up
regulate β receptors so symptoms of hyperthyroidism include increased heart
rate, increased blood pressure.
5. Together with human growth hormone and insulin, thyroid hormone accelerates
body growth, growth of nervous and skeletal system. Deficiency of thyroid
hormone during fetal development infancy childhood causes several mental
retardation and stunted growth.
Control of Thyroid hormone secretion:
1. Low blood level of T3 & T4 or low metabolic rate stimulates release of TRH
through hypothalamus.
2. TRH carried by hypophyseal portal vein to anterior pituitary to stimulate release
of TSH.
3. TSH released into blood stimulates thyroid follicular cells.
4. Thyroid follicle stimulates T3 & T4 release into blood by follicular cell.
5. Elevating the level of T3, inhibiting release of TRH and TSH.
Synthesis and secretion of T3 and T4
Formation, Storage, and Release of Thyroid occur as follows,
hormones: 1. Iodide trapping: thyroid follicular cells
The thyroid gland is the only endocrine gland that stores trap iodide ion by actively transporting
its secretory product in large quantities. them from the blood into the cytosol.
Figure 8: Synthesis and secretion of T3 and T4 occur 2. Synthesis of thyroglobulin: while the
as follows follicular cells are trapping iodine, they
are also synthesizing thyroglobulin (TGB),
a large glycoprotein that is produced in the
rough endoplasmic reticulum, modified in
Golgi complex, and packaged into
secretory vesicles. The vesicles then
undergo exocytosis, which release TGB
into the lumen of the follicle.
3. Oxidation of Iodine: Some of the
amino acid in TGB is tyrosine that will
become iodinated. However, -vely charged
iodide ions cannot bind to tyrosine until
they undergo oxidation (removal of
electrons) to iodine.
4.Iodination of tyrosine: As iodine
molecule I-2 from, they react with tyrosine
that are part of TGB Binding of one iodine
atom yields monoiodotyrosine (T1), and
second iodination produce diiodotyrosine
(T-2).the TGB with attached iodine atoms,
a sticky material that accumulates and is
stored in the lumen of thyroid follicle, is
termed colloid.
5.Coupling of T1-and T2 – during last
step of synthesis of thyroid hormone, two
T2 molecules joined together to form T-4
or one T1 and one T-2 to form T3.
6.Pinocytosis and digestion of colloid:
Droplets of colloid reenter follicular cells
by Pinocytosis and merge with lysosomes
breaks down TGB, cleaving off molecule
T-3and T-4.
7.Secretion of thyroid hormone Because
T3 and T4 lipid soluble, they diffuse
through plasma membrane into interstitial
fluid and then into the blood.T4 is
normally secreted in larger quantity than
T3.--T3 several times more potent than
T4.
8.Transport in the blood: More than
99% of both the T3and T4 combine with
transport proteins in the blood mainly
TBG.
Calcitonin produced by parafollicular cells of thyroid gland. Calcitonin decreases
the level of calcium in the blood by inhibiting the action of osteoclast, the cell that
breakdown bone extra cellular matrix. (Miacalcein).

THE PARATHYROID GLANDS

Figure: 9 Parathyroid gland and it microscopic struture

Parathyroid glands secretes parathyroid hormone.


• It is small, pea-shaped glands, located in the neck near the thyroid
• It is usually 4 - number can vary.
• It regulate the level of calcium in the body (osteoclast activity) and regulates
phosphate levels.
• It produce parathyroid hormone - ↑ level of calcium in blood
• Hypocalcaemia can result if parathyroids are removed or destroyed.
Figure 10: Regulation of Calcitonin and Parathhormone (PTH)

ADRENAL GLAND:
The paired adrenal (suprarenal) gland, one of which lies superior to each kidney,
has flattened pyramidal shape.
In an adult, each adrenal gland is 3-5 cm in height, 2-3 cm width, little less than 1 cm
thick, mass of 3.5-5 gm only half its size of birth.
During embryonic development, the adrenal glands differentiate into two structurally
and functionally distinct regions, a large, peripherally located adrenal cortex,
comprising 80-90% of the gland and a small centrally located adrenal medulla.
A connective tissue capsule covers the gland.
The adrenal cortex produces steroid hormones that are essential for life.
Complete loss of adrenocortical hormone leads to death due to dehydration and
electrolyte imbalance in a few days to week.
Adrenal medulla produces three catecholamine hormones, NE, Epinephrine and
small amount of dopamine.
Figure 11: Adrenal gland and its microscopic structure.

Adrenal cortex
It is subdivided into three zone each of which secretes different hormones.
The outer zone just deep to connective tissue capsule is the zona glomerulosa.
Its cell, which is closely packed and arranged in spherical clusters and arched
columns secrete hormones called mineralcorticoids because affect mineral
homeostasis.

Androgens

In both male and female, the adrenal cortex secretes small amounts of week
androgens.
The major androgens secreted by the adrenal gland are dehydroepiandrosterone
(DHEA).
After puberty in males, the androgens testosterone is also released in much greater
quantity by the testes.
In females, however, adrenal androgens play important role. They promote libido (sex
drive) and are converted into estrogen.
Adrenal androgens also stimulate growth of axillary and pubic hair in boys and girls;
contribute to the prepubertal growth spurt.
Adrenal medulla
It is modified sympathetic ganglion of ANS. The cell of adrenal medulla secrete
hormone. The hormone producing cells, called chromaffin cells.
Two major hormones synthesized by the adrenal medulla are epinephrine and
norepinephrine. It increases blood flow to vascular organ dilate airways to lungs.
Increased blood level of glucose and fatty acids.

Glucocorticoids

The Glucocorticoids, which regulates metabolism and resistance to stress, include


cortisol, corticosterone, and cortisone.
Control of glucorticoids secretion occurs via a typical negative feedback system.
Low blood levels of glucocorticoids, mainly cortisol, stimulate neurosecretory cells in
the hypothalamus, to secrete corticotrophin –releasing hormone (CRH).
CRH promotes the release of ACTH from the anterior pituitary.
ACTH flows in the blood to adrenal cortex, where it stimulates glucocorticoids
secretion.

Glucocorticoids have following effect:


1. Protein breakdown: it increases, the rate of protein breakdown, mainly in
muscle fibers, and thus increases the liberation of amino acid into the blood
stream.
2. Glucose formation: liver cell converts amino acid to glucose.
3. Lipolysis: breakdown of TG and release of fatty acids from adipose tissue.
4. Resistance to stress: They raise B.P. this effect may be advantageous in case
of sever blood loss.
5. Anti-inflammatory effect: Glucocorticoids inhibit WBC that participate in
inflammatory reponse.Unfortunately glucocorticoids also retards tissue repair.
6. Depression of immune response:-high dose of Glucocorticoids depress
immune response. it is useful in organ transplantation.
Pancreatic islets
The pancrease is both an endocrine gland and exocrine gland. The pancrease is made up
of small clusters of glandular epithelial cells. About 99% of clusters, called acini,
constitute the endocrine portion of organ.
The cells within acini secrete a mixture of fluid and digestive enzymes called pancreatic
juice. The remaining 1% cluster called pancreatic islets (Islet’s of langerhans from the
endocrine portion of pancreas )It is a flattened organ that measures about 12.5-15 cm in
length , the pancreases is located in the curves of duodenum , the first portion of small
intestine .
It consists of head, a body and a tail.

Figure 12: The Pancrease

Cell types in pancreatic islets: Each pancreatic islets includes four types of hormone
secreting cells.
• Alpha or A cells: Constitute about 17% of pancreatic islets and secrete glucagon.
• Beta or B cells : Constitute about 70% pancreatic islets cells secrete insulin .
• Delta cell about 70% of pancreatic islets cells and secrete somatostatin.
• F cells: Constitute the remainder of pancreatic islets cells secrete polypeptide
• Insulin lowers blood glucose by increasing the rate of glucose uptake and
utilization
• Glucagon raises blood glucose by increasing the rates of glycogen breakdown
and glucose manufacture by the liver.

Figure13: Regulation of insulin and glucagons secretion

Blood glucose level is the most important regulator of insulin and glucagons, several
hormones and neurotransmitter also regulates the release of these two hormones.

Insulin secretion is also stimulated by,


• Acetylcholine, the neurotransmitter liberated from axon terminals of
parasympathetic vagus nerves fiber that innervate pancreatic islets.
• The amino acids arginine and leucine , which would be present in blood at higher
levels after protein containing meal.
• Glucose dependent insulinotropic peptide (GIP) a hormone released by
enteroendocrine cells of small intestine in response to the presence of glucose in
the gastrointestinal tract.
Digestion and absorption of food containing both carbohydrate and protein provide
strong stimulation for insulin release.

Glucagon secretion is stimulated by,


Increased activity of the sympathetic division of the ANS , as occurs during exercise.
A raised in blood amino acids , if blood glucose level is low , which could occur after a
meal that contained mainly protein.
Ovaries and Testes
Gonads are the organs that produce gametes,
sperm in males, oocyte in females.
Ovaries , paired oval bodies located in the female pelvic cavity , produce several
steroidhormones, including two estrogens (estradiol and estrol) and progesterone.
Theses female sex hormones, along with FSH and LH from the anterior pituitary,
regulates the menstrual cycle, maintain pregnancy and prepare the mammary gland for
lactation.
They also provide enlargement of breast and widening of hips at puberty and help
maintain these female secondary sex characteristics.
The ovaries also produce inhibin, a protein hormone that inhibit secretion of FSH.
During preganancy , the ovaries and placenta produce a peptide hormone called relaxin
Relaxin increases the flexibility of pubic symphisis during pregnancy and helps dilate
the uterine cervix during labor and delivery.

Male Gonads
The testes are oval glands that lie in the scrotum.
The main hormone produced and secreted by the testes is testosterone, an androgen or
male sex hormone.
Testesterone develops and regulates sperm and stimulates the developments and
maintainance of male secondary sex characteristics, such as beard growth, deepening of
voice.
Testes also produce inhibin, which inhibits secretion of FSH.

Pineal gland
It is a small endocrine gland that attached to the roof of third ventricle of the brain at the
midline .
Part of the epithalamus , it is position between the two superior colliculi.
It has a mass 0.1-0.2 g and is covered by capsule formed by the pia matter.
The gland consists of masses of neuroglia and secretory cells called pinealocytes.
Pineal gland secrete melatonin , an amine hormone derived from serotonin, and that
more melatonin is released in darkness and less in strong sunlight.
In darkness, norepinephrine released by the sympathetic fibers, stimulates, synthesis and
secretion of melatonin which promote sleepiness.
Melatonin is thought to contribute to setting the body’s biological clock, which is
controlled from the suprachiasmatic nucleus of the hypothalamus.
During sleep melatonin level is increased tenfold and then decline to a low level again
before awakening.
Melatonin is also potent antioxidant that may provide some protection against damaging
oxygen free radicals.

Thymus
It is located behind the sternum between the lungs.the hormone produced by the
thymus,-thymosin, thymic humoral factor(THF), thymic factor(TF) and thymopoietin
promote maturation of T-cells and may retard aging process.`