Endocrine Notes
Endocrine Notes
Hormones are chemical substances produced by ductless glands in minute quantities which
upon reaching the target organs via circulation produce the desired effect. The term
Hormone was coined by Bayliss and Starling in 1905.
The peripheral nervous system and endocrine glands are the two integrative units that are
under the rigorous control and coordination of the Central Nervous System. Even though
anatomically distinct, they are functionally intimately related, therefore called Neuro-
Endocrine system. The distinction between a hormone and a neuro humor is not rigid. For
example, when adrenaline is secreted by adrenal medulla, it is called a hormone. When it is
secreted by synaptic neurons from their axon tips, it is called a neuro humor.
Neuro humors are also produced by neuro secretory neurons of the hypothalamus. It
produces two types of neuro humors. The first type are stored in the neurohypophysis and
released into circulation as hormones. The other type referred to as ‘release factors’ are
released into hypothalamo - hypophyseal tract and reach the pitutary. Hypothalamus being
well connected to all parts of the brain through nerve tracts mediates between the endocrine
system and nervous system by modulating of the pitutary secretions via production of
‘release factors’. The release factors upon reaching the pituitary gland via hypothalamo -
hypophyseal tract, elicit production and /or release of respective hormones. Pituitary is thus
called ‘The band master of endocrinal orchestra’.
Pitutary gland:
1. Adenohypophysis : a. Acidophil cells / Eosin stains (43%) - Produce STH, Prolactin
b. Chromophobe cells (50%) – Mother cells for both
c. Basophil cells (7%)-Produce FSH, LH, TSH & ACTH
The cells producing hormones are granular while chromophobes are not.
2. Intermediate lobe – Polygonal cells – Melanotrophs – MSH
3. Neurohypophysis – a. Pituticytes – large branching cells – Pigmented and granular
b. Non- medullated Nerve fibers.(Oxytocin and vasopressin
are released from the posterior pitutary)
Dwarfism results due to STH deficiency in children. They are also called midgets. The
body of the man is proportionate, but child sized and with no sec. sexual characters.
The condition is not fatal.
Gigantism is over growth resulting from hyper secretion of STH. The growth may be
proportionate. Man grows to 9 ft in height. Usually he cannot survive due to disturbed
physiology upon reaching late adolescence.
Acromegaly results when there is hyper secretion of STH in adults. The cheek bones, jaws,
toes and fingers begin to grow once again leading to disproportionate appearance. However
it is not fatal.
STH has a synergistic function. TSH, ACTH, LH, FSH are less effective in case of
Somatotropic hormone deficiency. Probably it creates a responsive environment for these
hormones to act. Permissiveness means that this hormone is necessary for other hormones
to act normally.
5. Follicle stimulating hormone (TSH): Glycoprotein. Mol. wt. 30,000 – 67,000. It acts on
the follicles of the ovary to regulate their development up to release of egg from ovary. It
also acts on the granulose cells of the ovary to produce estrogen needed for maintenance of
sec. sexual charecters. Further, it acts on the spermatid cells and is very much responsible
for the process of spermatogenesis. Its failure severely affects normal development of egg
and sperms.
Hormones of Neurohypophysis:
1. Anti-diuretic hormone (ADH) / Vasopressin: It is an octa peptide. Mol. wt. 1000 (approx)
It is produced by supra-optic nuclei and stored in neurohypophysis. It has a pronounced
effect on the epithelial cells of the distal convoluted tubule and collecting ducts in the
kidney causing reabsorption of water. Production of hyper osmotic urine by kidney is under
the direct influence of ADH. When hypothalamic lesions occur destroying the secretory
neurons or the hypothalamus or hypophyscial tract, the result is production of very large
quantities of extremely dilute urine. It is called Diabetes Insipidus. The condition can be
corrected by injecting Vasopressin.
An injection of ADH in to amphibians, reptiles or birds causes ‘Brunn’ effect. The animal
shows marked increase in weight on account of increased water reabsorption by kidney
tubules as well as an increase in uptake by skin also.
Another important function is its effect on the smooth muscles of the blood vessels. It
causes contraction leading to an increase in Blood pressure.
Thyroxin is an Iodinated protein (Mol. wt. 680,000). It is stored in the thyroid gland
bound to a globulin protein to form Thyroglobulin. Iodine is the most important
component of thyroxin. Hence it is highly conditioned by iodine supply (1 mg / week
is needed in diet of an adult). Usually iodized salts are the best source. The thyroid cells
have the capacity to actively take up and concentrate iodine in either its elemental form
or in an oxide form. This is possible because of the iodine pump in the cells of the
thyroid gland.
The active forms of thyroxin are Tri-iodothyronine (T3) and tetra-iodothyronine (T4).
The ratio of the two is 14:1. T3 is short-lived but several times more potent that T4. A
deiodinase reaction in liver converts T4 to T3. The hormone is always bound to specific
binding proteins of the plasma (globulins) and transported to various tissues.
Thyroxin acts on the enzymes of mitochondria. Anabolic processes involving glucose,
fats, proteins and vitamins also need it. Thyroxin controls BMR. It is required for
normal development and function of reproductive organs. It is also important for
skeletal growth and tissue differentiation.
Hypothyroidism in man is caused due to impairment of thyroxin synthesis. When this
happens in children it results in Cretinism whereas the same, in adults causes
Myxedema.
Cretinism is characterized by arrested growth, and flabby body. The children are
mentally defective and have low IQ. Skin becomes pale, thick and dry/coarse. They
remain sexually under developed. If the abnormality is caused due to dietary deficiency
of iodine, the same can be corrected by exogenous supply. If it is from the time of birth,
there is no cure.
Myxedema is characterized by low body temperature, mental depression and very low
BMR. The person becomes dull and lethargic. If he is administered thyroxin, he once
again becomes normal. Simple goiter is the classical manifestation of hypothyroidism.
Deficiency of iodine in diet causes this disorder. Sub- Himalayan tracts, Central Europe,
regions around Ural Mountains are iodine deficient in their natural water sources.
Further, PTH acts on the kidney epithelial cells and increases resorption of Ca2+ ions
from the urinary filtrate. Hyperphopatamia caused due to PTH action is corrected by
vitamin D by a separate mechanism. PTH has a secondary role in calcium uptake from
the intestine. Vitamin D (1,2-Dihydroxy Cholecalciferol) functioning as a hormone is
primarily responsible for intestinal Ca2+ uptake.
Control of PTH: A negative feedback control mechanism exists between PTH and
circulating levels of Ca2+ as is evident from its hyper-activity under conditions of
hypocalcaemia and hypo-activity under conditions of hypercalcaemia. PTH is not
controlled by secretions of the pituitary gland.
Thyroid-Parathyroid complex:
In lower vertebrates Thyrocalcitonin (TCT) is produced by Ultimobranchial glands. It
is a hypocalcaemia factor. PTH and TGT are antagonists. TCT is distinct from
Thyroxin and is basically a polypeptide. The exact source is controversial but recent
studies suggest that it is produced by Para follicular or “C” Cells of thyroid in higher
vertebrates in response to a release factor secreted by parathyroid glands.
Pancrease:
It is both an Endocrine and an Exocrine gland. A million or more lobes are scattered
throughout the gland. Islets of Langerhans are interspersed among acini of the Pancreas.
The islets have a rich supply of blood capillaries and sinusoids.
α – cells – Glucagon – hyper glycemic factor
β – cells – Insulin – hypo glycemic factor
µ - cells – No function identified so far.
Both hormones act on liver as it is the storage organ of glycogen and an important site
of carbohydrate metabolism. Normal glucose levels in human serum is 80 - 120mg / dl.
Insulin: Polypeptide with two chains A and B. A chain has 21amino acids where as B
chain has 30 amino acids. Mol.wt. is ≈ 5735 (Ox insulin)
Under hypoglycemia, β cells secrete more insulin to normalize the conc. of glucose in
blood plasma. The glucose concentration is lowered by insulin in the following ways:
1. Altering permeability of tissue cells to glucose by acting on their cell membranes
2. Excess glucose is converted into some other substance(s), mainly glycogen in liver
and muscles cells by glycogenesis.
3. Increase in cellular oxidation of glucose in the tissue (G-6-P)
4. Increase the liver capacity to store very high conc. of glycogen. An over dose of
insulin can suppress the glucose concentration to 40 mg/dl leading to hypoglycemic
shock and even death.
Glucagon: Strait chain polypeptide containing 29 Amino acids and has a Mol. wt. of ≈
3485. There are no disulphide bonds in the molecule.
Under hypoglycemic conditions α cells secrete more glucagons to enhance glucose
levels in the blood by acting mainly on liver. Glycogenolysis (break down of glycogen
to release glucose) leads to normalcy of glucose levels. It probably acts on the
phosphorylase involved in converting glycogen to glucose-1-phosphate which is the
rate limiting step.
Adrenal gland:
There are a pair of adrenal glands one on each kidney (supra renal glands). All
hormones of adrenal gland are steroids. The gland can be divided into two regions:
1. Outer Cortex that develops from neural crest.
2. Inner medulla that develops from mesodermal cells.
Adrenal cortex: It has 3 regions:
1. Zona glomerulosa which secretes mineralocorticoids involved in mineral metabolism.
2. Zona fasiciculata as well as Zona reticularis secrete glucocorticoids which are
anti inflammatory hormones. They influence glucose metabolism.
3. Zona reticularis in addition secretes sex hormones in very small quantities
I. Zona glomerulosa is Not under the influence of ACTH. It functions under the
influence of adrenoglomerulotropin produced from pineal body and angiotensin – I
from kidney. It secretes two mineralocorticoids:
(1) Aldosterone and (2) 2-Deoxycorticosterone – Both regulate electrolyte and water
balance. The two hormones influence sodium retention and concurrent potassium
excretion in urine by acting on the distal convoluted tubule. Consequently, there is an
increase in osmotic pressure of blood resulting in an increased water retention and
increased blood pressure.
II. Zona fasciculate (and zona reticularis) produce two glucocorticoids – Cortisol and
Corticosterone. They are anti inflammatory hormones which suppress inflammation.
The two hormones primarily act on the liver where they enhance conversion of proteins
and fat into carbohydrates through a process of Gluconeogenesis.
Acting in conjunction with Adrenaline / Epinephrine and Glucagon, Cortisol converts
glycogen to glucose through a process of glycogenolysis in liver and muscle cells. In
other words, it is antagonistic to insulin and increases blood glucose levels. During
fasting even without under going any increase in concentration, it activates lipolysis
leading to an increase in blood glucose levels. These two hormones act selectively
influencing Glycogenesis and / or Gluconeogenesis in order to maintain normal blood
glucose levels. They have the same effect like that of aldosterone i.e., retention of
sodium with simultaneous excretion of potassium. However, Cortisol along with other
glucocorticoids is antagonistic to ADH in renal tubules i.e., it increases water excretion.
III. Zona reticularis produces sex hormones. Since they are produced in very small
quantities, their role in an adult is negligible. In any case, sex organs themselves
produce many of these hormones in large volumes.
IV. Selye’s concept of stress effects:
Stress activates pituitary – adrenal axis with subsequent release of steroids which
enable animals to withstand stress. The hypothesis is that the adaptive mechanisms
during exposure of the animal to stress on one hand helps the animal to withstand stress
and on the other makes it susceptible to infections due to weakened immunological
abilities leading to disease. Glucocorticoids secreted mainly by zona fasciculate are
controlled by adenohypophysis. The hypothalamus releases the corticotrophin releasing
factor (CRF) which acts on pituitary producing ACTH. This release is in response to a
condition of stress perceived by hypothalamus either through Nervous stimulus or
Release of catecholamine (adrenaline / nor adrenaline etc.) by the adrenal medulla
under stress.
Adrenal medulla:
The hormones produced by it are called ‘emergency hormones’ preparing the animal
for ‘fight or flight’. They are produced by chromaffin cells. The medulla produces
Adrenaline (Epinephrine) and Nor adrenaline (Nor Epinephrine). The most important
function of these hormones is to promote glycogenolysis in liver and muscle tissues and
bring about hyperglycemia. Glucose is needed for production of additional energy
during fight or flight. The general actions of these hormones are:
Increase in heart beat, cardiac output and blood pressure leading to efficient circulation;
Additional flow of blood to brain and muscles and decreased flow of blood to skin to
prevent excessive bleeding in case of injury; Dilatation of pupils and bronchi.
The two hormones, epinephrine and nor epinephrine are also called as Catecholamines.
The adrenal medulla is under the influence of the higher nervous system represented by
cerebral hemispheres, mid brain and hypothalamus through the sympathetic system.
The two hormones are quite similar structurally and biologically. However, epinephrine
has an additional methyl group in side chain. The two hormones are released
independently and perform distinct functions. Epinephrine promotes hyperglycemia, by
increasing of blood flow to vital organs like muscles, brain and liver there by preparing
the animal to meet emergency. On the other hand nor epinephrine has a generalized
vasoconstrictory effect and increases the blood pressure (Exception: Coronary artery).
The unique ness of the secretions of adrenal medulla is that they act as a sympathetic
system for those structures which are not innervated by nerves directly. This brings
about a general enhancement of metabolic functions in all important organs there by
preparing the body to meet the emergency and sustain it.
Pineal body:
It is a small, flattened, cone shaped structure attached to the roof of the third ventricle
by a stalk deep inside the brain. Pineal body secretes Melatonin which is antagonistic to
MSH. It brings about concentration of melanin in melanophores leading to bleaching
under light. Melatonin is controlled by photoperiod. In summer and spring when light
intensity is high, the secretion falls thereby lifting its inhibitory effect on the gonads.
This leads to faster maturation and sexual urge. Hence, in humans the destruction of
pineal gland or its pathology causes precocious puberty.
Thymus gland:
It is not an endocrine gland. It is involved in immunological functions during childhood
years. It is the location where proliferation & differentiation of lymphocytes takes place.
NEURO SECRETION
Neuro secretary cell or neuron is also a neuron in all respects except that it has the
additional ability to respond to afferent stimuli and release hormones / neuro humors as an
efferent response. The presence of neuro secretory granules and an elaborate axonal system
ending in close association with blood capillaries or sinusoids are important features. The
granules are membrane bound vesicles. They get stained with certain special stains.
The synthesis and secretion of neuro hormones has three steps:
1. The synthesis of neuro secretory material: A well developed Endoplasmic reticulum and
Golgi bodies indicates that the neuro secretory material is produced in the Perikaryon
(around nucleus) region. The Golgi apparatus concentrates these materials and packs them
in to membrane bound vesicles.
2. Axonal transport of neuro secretory material: the vesicles are moved from the site of
synthesis to site of secretion by a process of axo plasmic flow. Presence of stained
secretory material in axons just like a string of pearls and their accumulation near the site
of release is ample proof of the transportation process.
3. Release of neuro secretory material: The material is released from the axonal end bulb of
the neuron. There are three views about it.
a. Neurosecretion passes out as an intact granule / vesicle.
b. Neurosecretion released by reverse pinocytosis / exocytosis.
c. Neurosecretion diffuses through the axonal membrane.
2. Lipid-insoluble hormones which do not enter in to the target cell. Instead they bind
to cell surface receptors and as a consequence produce one or more ‘Second
messengers’ that mediate the responses in the cell. The second messenger binds to
an internal regulator that controls various effectors like plasma membrane, micro
tubules, enzymes etc., responsible for actual cell responses that are short term
effects lasting for many seconds to a few hours only. Eg: Catecholamine like
epinephrine and nor epinephrine; Peptide hormones like ACTH and insulin, that
have response times lasting for several seconds and a few hours respectively.
Second messenger and intra cellular signaling: There are three important categories of
secondary messengers – 1. cAMP and cGMP; 2. Phospholipids; 3. Ca2+ ions.
Often cAMP is taken as an example for outlining the mechanism. The hormone molecule is
the primary messenger. It binds to the specialized cell surface receptor. This interaction
produces a transducer molecule in the cell membrane. It in turn produces an amplifier
molecule that amplifies the signal. This in turn activates membrane bound adenylate
cyclase that converts ATP in to cAMP and releases it in to the cytoplasm. The second
messenger (cAMP) interacts with the internal regulator protein kinase A and brings about
the desired response in a variety of ways. The figure illustrates the sequence of events:
The receptors are different for stimulatory and inhibitory signals respectively. When a
single signal brings about two responses it is Divergence and when two separate signals
bring about the same response it is Convergence. Also because of the amplifiers a few
primary messengers (hormone molecules) are sufficient to produce perceptible effects.
The mode of action a hormone can be Direct. Here the hormone interacts directly with the
specific genes after combining with receptor.
Hormonal action on Genes: The hormones act on the genes directly either activating them
or suppressing them. This concept finds an example in the hormone of insects which
control the metamorphosis from larval stage to pupa stage. The hormone is Ecdysone
(produced in the prothoracic glands). Coinciding with increase in the hormone
concentration, the salivary cell chromosomes show visible puffs at certain places. These
puffs have been identified as sites of transcription. Protein synthesis followed subsequently.
The mode of action a hormone can be Indirect. Here the hormonal action is mediated
through the involvement of cytoplasmic regulator.
a. Action on enzyme systems of a cell: Hormones exert action even at minutest
concentrations. Epinephrine and glucagone bring about activation of phosphorylase
enzyme system involved in glycogenolysis in liver and muscle cells. So also insulin
selectively influences hexokinase enzyme involved in glycogenesis in the liver cells.
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