in this slide u are able to well known about the introduction of hormones.
categories, classification, function, structure, regulation, location, mechanism of action, how hormone regulates our body function, how it maintains the homeostasis condition.
structure of hormones.
4. Introduction:
Secretions by means of duct – exocrine
Secretions by means of ductless & into the blood stream – endocrine – said to be as hormones.
DEFINITION:
It is a chemical substance which is produced in one part of the body, enters the circulation and is
carried to distant target organs and tissues to modify their structures and functions.
hormones – stimulating substance and act as body catalyst.
Hormone derived from Greek word harmacin – to excite.
Despite varying actions depending on the target organ.
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5. 1. They are chemical entities produced by special cells of endocrine glands.
2. They are transported to the target cells/ tissue/organ via circulation.
3. Their actions are species specific…
4. They are active in very minute quantities.
5. They are mostly water soluble.
6. They are low in molecular weight.
7. They are destroyed after their actions.
8. Chemically they are heterogeneous substances.
9. They cannot be stored for a longtime; usually they are synthesized and secreted during the time of
requirement.
10. They usually activate target cells by forming hormone receptor complex.
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8. Dissimilarities of Hormone and Enzyme:
• They are produced in an organ other than that in which they ultimately perform their action.
• They are secreted in blood prior to use.
• Structurally they are not always proteins. Few hormones are protein in nature, few are small
peptides.
*Some hormones are derived from amino acids while some are steroid in nature.
Similarities of Hormone and Enzyme:
• They act as body catalysts resembling enzymes in some aspect.
• They are required only in small quantities.
• They are used up during the reaction.
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9. Classification of Hormones:
1. Steroid hormones:
These are steroid in nature such as adrenocorticosteroid hormones, androgens,
oestrogens and progesterone.
2. Amino acid derivatives:
These are derived from amino acid tyrosine, e.g. epinephrine, norepinephrine and
thyroid hormones.
3. Peptide/Protein hormones:
These are either large proteins or small or medium size peptides, e.g. Insulin,
glucagon, parathormone, calcitonin, pituitary hormones, etc.
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10. Factors Regulating Hormone Action
Action of a hormone at a target organ is regulated
by four factors:
1. Rate of synthesis and secretion: The hormone is
stored in the endocrine gland.
2. In some cases, specific transport systems in
plasma.
3. Hormone-specific receptors in target cell
membranes which differ from tissue to tissue, and
4. Ultimate degradation of the hormone usually by
the liver or kidneys.
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13. CHEMISTRY:
Molecular weight: 21500 Da
191 amino acids
Two disulfide bridges between the adjacent cysteine residues (53 and 165 and 182 and 189).
A high degree of similarity in the amino acid sequences of human, bovine and porcine GH;
METABOLIC ROLE:
1. Protein synthesis:
By positive nitrogen balance,
Stimulates overall protein synthesis by retention of phosphorous
Reabsorption of blood amino acid and urea level are decreased so facilitates entry of AA into the cell.
GH increases DNA & RNA synthesis & collagen.
2. Lipid metabolism:
Bring out lipolysis in adipose tissues by triacylglycerol lipase.
3. Carbohydrate metabolism:
Diabetogenic hormone.
Higher GH cause Hyperglycaemia, glycosuria.
Higher GH cause increased amount of insulin & glucagon.
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14. 4. EFFECT ON GROWTH OF BONES:
Higher concentration prolonged growth of epiphyseal cartilages to cause over growth of long
bone.
Acromegaly in adults.
Promotes retention of calcium and phosphate in ossification and osteogenesis.
5. PROLACTIN ACTION:
GH binds to membrane receptors for prolactin and stimulates the growth and enlargement of
mammy glands.
6. ION OR MINERAL METABOLISM:
Intestinal absorption of calcium.
Retains Na, Ca, K, Mg.
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16. CHEMISTRY:
This is a monomeric simple protein (MW 23,000).
It contains 199 amino acids with three –S–S–linkages.
It is secreted by lactotroph α-cells of anterior pituitary and
As already mentioned has sequence homology with growth hormone.
METABOLIC ROLE:
1.To stimulate mammary growth and the secretion of milk – by specific glycoprotein receptors on plasma
membrane of mammary gland – stimulates the mRNA synthesis leads to enlargement of breasts during
pregnancy this called as mammotrophic action.
2.Synthesis of milk protein like lactalbumin, casein after partnutrition is called as lactogenic effect.
3.estrogens, thyroid hormones and glucocorticoids increase the number of prolactin receptors on the mammary
cell membrane.
4.Progesterone has the opposite effect.
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18. CHEMISTRY:
Produced by basophil cells of anterior pituitary.
Glycoprotein in nature.
Mol.wt. 30,000Da
Consists of a and b sub units.
The ά subunit of TSH, LH, HCG, FSH are nearly identical.
The ά subunit have 92 amino acids.
The β subunit has 112 amino acids.
Several disulfide bridges.
Its carbohydrate content is 21%.
The two chains are linked by N-glycosidic linkages to asparagine residues.
METABOLIC ROLE:
There are glycoprotein receptors on the thyroid cell membrane which bind to the β subunit of TSH leads to
activates the complex of adenylate cyclase catalyses the formation of c-AMP which act as 2ND messenger
for TSH hormones.
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19. • The TSH stimulates the synthesis of thyroid hormones at all stages such as Iodine uptake,
organification and coupling.
• It enhances the release of stored thyroid hormones.
• It increases DNA content, RNA and translation of proteins, cell size.
• It stimulates glycolysis, TCA cycle, HMP and phospholipid synthesis. Stimulation of last
two does not involve c-AMP.
• It activates adipose tissue lipase to enhance the release of fatty acids (lipolysis).
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21. CHEMISTRY:
Single polypeptide – 39 amino acids.
Mol.wt. 4,500Da.
Two forms – ά & β corticotrophin.
Biological activity of ACTH in the first 23 amino acids from the N-terminal end.
The structure resembles to LPH, MSH, endorphins.
PMOC – pro-opiomelano cortin peptide.
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22. METABOLIC ROLE:
• ACTH is found to increase the transfer of cholesterol from plasma lipoproteins into the fasciculata
cells.
• The ACTH induces rise in c-AMP, brings about phosphorylation and activation of cholesterol esterase.
The enzyme action ultimately makes a large pool of free cholesterol.
• Corticotropin promotes the binding of cholesterol to mitochondrial cytochrome P450 required for
hydroxylating cholesterol.
• It activates the rate limiting enzyme for conversion of cholesterol to pregnenolone.
• It activates dehydrogenases of HMP to increase the conc. of NADPH required for hydroxylation.
• Direct effects on carbohydrate metabolism include:
• Lowering of blood glucose ↓;
• Increase in glucose tolerance;
• Deposition of glycogen in adipose tissue is increased, regarded as due to stimulation of insulin
secretion.
• It has MSH activity due to homology in amino acid sequence.
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23. Pituitary Gonadotropins
These tropic hormones influence the function and maturation of the testes and ovary and are of two types:
• Follicle Stimulating Hormone (FSH)
• Luteinising Hormone (LH)
CHEMISTRY:
Both are glycoproteins with sialic acid, hexose, hexosamine as a carbohydrate moiety (16%).
Mol.wt. of FSH – 25000 Da, LH – 40000 Da.
They are dimers ά , β subunits are interlinked non – covalently.
The ά chain is identical for TSH, FSG, LH.
The β chain of FSH and LH is 118 and 112 amino acids respectively.
Have several disulfide bridges.
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25. Metabolic Role of FSH
It brings about its action by specific receptor binding and c-AMP.
In females:
• It promotes follicular growth
• Prepares the Graafian follicle for the action of LH and
• Enhances the release of estrogen induced by LH.
In males:
• It stimulates seminal tubule and testicular growth, and
• Plays an important role in maturation of spermatozoa.
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Metabolic Role of LH
This hormone is also known as interstitial cells stimulating hormone (ICSH).
In females:
• It causes the final maturation of Graafian follicle and stimulates ovulation.
• Stimulates secretion of estrogen by the theca and granulosa cells.
• It helps in the formation and development of corpus luteum for luteinisation of cells.
• In conjunction with luteotropic hormone (LTH), it is concerned with the production of
estrogen and progesterone by the corpus luteum.
• In the ovary it can stimulate the nongerminal elements, which contain the interstitial cells to
produce the androgens, androstenedione, DHEA and testosterone.
27. HORMONE OF MIDDLE LOBE OF PITUITARY
Melanocyte Stimulating Hormones:
The hormones secreted by intermediate lobe or middle lobe of pituitary gland are called
melanocyte-stimulating hormones or MSH.
POMC is the precursor molecule which is cleaved by proteases to give ACTH and β-lipotropin.
The ACTH is further cleaved to β-MSH which has 13 amino acids.
There is also α-MSH which is present in larger quantities.
Amino acids 11-17 of β-MSH are common to both α-MSH and ACTH.
MSH darkens the skin and is involved in skin pigmentation by deposition of melanin by
melanocytes.
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29. HORMONES OF POSTERIOR PITUITARY LOBE
They are:
1. Vasopressin (Pitressin) or Arginine Vasopressin (ADH) Anti-Diuretic Hormone and
2. Oxytocin.
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30. Both are small peptides containing 9 amino acids. Oxytocin differs from Vasopressin with respect to 3rd and 8th
amino acid residues.
Their biological activities depend on C-terminal glycinamide, the side chain amide groups of glutamine and
asparagine, the hydroxyphenyl group of tyrosine, and
The intra-chain –S–S–linkage between cysteine of Ist and 6th amino acid.
Molecular Weight. 1007.2 Da of Oxytocin, 1056.2 Da.
METABOLIC ROLE OF VASOPRESSIN:
1. Antidiuretic action:
Antidiuretic effect is its main function.
It reabsorbs water from the kidneys by distal tubules and collecting ducts.
It is found to be mediated through formation of c-AMP.
It is released due to rise in plasma osmolarity.
This leads to formation of hypertonic urine having low volume, high sp. gr. and high conc. of Na+, Cl–, phosphate
and urea.
Halothane, colchicine and vinblastine inhibit antidiuretic effect of vasopressin.
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31. 2. Urea-retention effect:
Permeability of medullary collecting ducts to urea is increased by vasopressin.
This leads to retention of urea and subsequently contributes to hypertonicity of the medullary interstitium.
Urea retention effect can be reversed by phloretin.
3. Pressor effect:
It stimulates the contraction of smooth muscles and thus causes vasoconstriction by increasing cytosolic
Ca+2 concentration.
4. Glycogenolytic effect:
By increasing intracellular calcium concentration.
Effect of calcium on Glycogenolysis
These results indicate that activation of glycogen phosphorylase by K+ or veratridine occurs by a cyclic
AMP-independent and calcium-dependent mechanism.
The calcium dependency of brain phosphorylase kinase renders this kinase the prime target enzyme
for regulation of glycogenolysis by calcium ions.
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32. METABOLIC ROLE OF OXYTOCIN:
Contraction of smooth muscle is the primary function of oxytocin.
There are basically two effects, one on mammary glands called as galactobolic effect and the other on uterus
called as uterine effect.
1. Galactobolic effect:
This is released due to neuroendocrinal reflex such as suckling of nipples. By doing so it causes the
contraction of myoepithelial cells around mammary aleveoli and ducts and the smooth muscles surrounding the
mammary milk sinuses; estrogen increases the number of oxytocin receptors during pregnancy while
progesterone decreases the same and also inhibits the secretion of oxytocin.
2. Uterine effect:
It is found to be elevated at full term pregnancy. It causes contraction of uterine muscle for child-birth.
Estrogens enhance while progesterone decreases oxytocin receptors as well as its secretion. Oxytocin is also
secreted during coitus by the female uterus which promotes the aspiration of semen into the uterus. This is also
augmented by rise in estrogen in the follicular phase of menstrual cycle.
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34. Hormones Produced by Thyroid Gland:
1. Follicular cells: Produces T4, T3 and
“reverse” T3
2. Parafollicular C-cells: Produces
calcitonin (hence also called
thyrocalcitonin).
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35. Two raw materials
(substrates) required by
thyroid gland to synthesis the
thyroid hormones are:
1. Thyroglobulin
2. Iodine
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. About 80-95 µg of thyroxine is secreted daily under
normal physiological conditions.
37. Chemistry of Thyroid Hormones:
The hormones T4, T3 and “reverse” T3 are iodinated amino acid tyrosine.
The iodine in thyroxine accounts for 80 per cent of the organically bound iodine in thyroid venous
blood.
Small amounts of ‘reverse’ tri-iodo thyronine, Monoiodotyrosine (MIT) and other compound are
also liberated.
T3 versus T4:
Although the circulating levels of T3 are much lower than the corresponding T4 levels, T3 appears
to be the major thyroid hormone metabolically.
Characteristics of T3
• Extrathyroidal de-iodination converts T4 to T3
• T3 binds to the “thyroid receptor” in target cells with 10 times the affinity of T4
• About 80 per cent of circulating T4 is converted to T3 or reverse T3 (r T3) in the periphery
• T3 is loosely bound to serum proteins
• T3 is 3 to 5 times more active than T4
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38. • Has a more rapid onset of action
• It is also more rapidly degraded in the body.
Note:
• ‘Reverse’ T3 (r T3) is a very weak agonist that is made relatively in larger amounts in chronic diseases, in
carbohydrate starvation and in foetus.
• Propylthiouracil and propranolol decrease the conversion of T4 to T3.
Chemical Hyperthyroidism:
In rare subjects with chemical hyperthyroidism, in whom circulating level of bound and free T4 is normal, the
T3 concentration is elevated and accounts for the thyrotoxic state.
In these patients, significant amount of T3 probably arises by de-iodination of T4 at peripheral level.
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39. METABOLIC ROLE OF THYROID HORMONES:
Effects on Protein Metabolism:
• In hypothyroid children and in physiological doses, thyroid hormones when given in small doses, favour
protein anabolism, leading to N-retention (+ve N-balance), because they stimulate growth.
• Large, unphysiological doses of thyroxine, cause protein catabolism, leading to –ve N-balance.
CLINICAL SIGNIFICANCE:
The catabolic response in skeletal muscle, in cases of hyperthyroidism, is sometimes so severe that muscle
weakness is a prominent symptom and creatinuria is marked, called thyrotoxic myopathy.
The K+ liberated during protein catabolism appears in urine and there is an increase in urinary hexosamine
and uric acid excretion.
Effects on bone proteins:
Mobilisation of bone proteins leads to hypercalcaemia and hypercalciuria, with some degree of osteoporosis.
Effect on skin:
The skin normally contains a variety of proteins combined with polysaccharides, hyaluronic acid and
chondroitin sulphuric acid.
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2. Effects on Carbohydrate Metabolism:
Net effect on carbohydrate metabolism:
• Increase in blood sugar ↑ (hyperglycaemia), and glycosuria
• Increased glucose utilisation, and decreased glucose tolerance.
Thyroid hormones are, therefore, antagonistic to insulin.
• Thyroid hormones increase the rate of absorption of glucose from intestine.
• Decreased glucose tolerance may be contributed to also by acceleration of degradation of insulin.
3. Vitamins:
• Administration of large amounts of thyroid hormones increase the requirement of certain members of
vitamin B-complex (thiamine, pyridoxine, pantothenic acid) and for vitamin C. These are presumably
related to the stimulation of oxidative and catabolic processes.
• Thyroxine is necessary for hepatic conversion of carotene to vitamin A and the accumulation of
carotene in the bloodstream (“carotinaemia”) in hypothyroidism is responsible for yellowish tint of the
skin.
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CLINICAL IMPORTANCE
Iodide therapy
is sometimes done by surgeons
to hyperthyroid patients for a short
interval to prepare the patient for
surgery (subtotal thyroidectomy).
Advantages
• Colloid accumulates and
enhances firmness to the gland
• Vascularity of the gland
is decreased
• Decreases the blood
thyroid hormone level
• Reduces the chance of
acute postoperative
hyperthyroidism.
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Calcitonin is a calcium regulating hormone.
It is proved that calcitonin originates from special cells, called “C-cells”, parafollicular cells.
C-cells constitute an endocrine system which, are derived from “neural crest” and are found in
thyroid, parathyroids and in thymus.
CHEMISTRY:
• A single chain lipophilic polypeptide.
• Mol.wt. 3600Da
• 4 separative fractions (ά, β, ɣ, δ –calcitonin)
• Contain 32 amino acids.
• N- terminal is cysteine, C-terminal is prolinamide.
• Interchain disulfide bridge between position 1 and 7.
• High content of aspartic acid and threonine.
• Isoleucine and lysine are absent.
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METABOLIC ROLE:
Calcitonin acts both on
(a) bone and
(b) kidneys.
Indirectly, the effects of these two organ systems account for:
• Hypocalcaemia and
• Hypophosphataemia.
(b) Action on Kidneys:
• The hormone acts on the distal tubule and ascending limb of Loop of Henle and decreases tubular
reabsorption of both calcium and inorganic PO4 thus producing calcinuria and phosphaturia.
• The hormone inhibits α-1-hydroxylase and inhibits synthesis of 1,25-di-OH-D3 thus
decreasing calcium absorption from intestine.
Both the above effects account for hypocalcaemia.
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Insulin is a protein hormone, secreted by β-cells of islets of Langerhans of pancreas.
Minimum calculated molecular wt. is 5734.
‘polymeric’ forms (dimers, trimers, etc.) depending on pH, temperature and concentration
Insulin from Other Species:
Porcine insulin:
Porcine insulin is similar to human insulin. It differs by only terminal amino acid No.-30 of B-
chain.
• In humans: It is threonine.
• In porcine: It is alanine in place of threonine.
Removal of alanine (de-alaninated) retains the biologic activity.
A normal measurement of free insulin is less than 17 mcU/mL.
Hyperinsulinemia - type 2 diabetes
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Glucagon is a hormone produced by α-cells of islet of Langerhans of pancreas and is an important hormone
involved in:
• Rapid mobilisation of hepatic glycogen to give glucose by glycogenolysis, and
• To a lesser extent FA from adipose tissue. Thus, it acts as a hormone required to mobilise metabolic
substrates from storage depots
Chemistry
Glucagon has been purified and crystallised from pancreatic extracts and also the hormone has been
synthesised.
It is a polypeptide containing 29 amino acids. There are only 15 different amino acids in the
molecule.
Amino acid sequence has been determined, histidine is the N-terminal amino acid and threonine is
the C-terminal.
Molecular wt. is approx. 3485
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Unlike Insulin:
• It does not require Zinc or other metals for its crystallisation.
• Glucagon contains no cystine, proline or isoleucine, but contains tyrosine, methionine and
tryptophan.
The normal range is 50 to 100 pg/mL.
Hyperglucagonemia - are in excess of 500 pg/mL.
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According to structure:
Adrenocortical hormones are mainly of two structural types:
1. C-21 steroids: Those which have a two carbon side chain at position 17 of the ‘D’ ring and contain total
21 carbon atoms.
2. C-19 steroids: Those which have an O2 atom or – OH group at position 17 and contain 19 carbon atoms.
Most of the C-19 steroids have a = 0 group at position 17 and are, therefore, called as “17- oxosteroids” (17-
ketosteroids).
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ESTROGENS
• Growth of female genital organs,
• The appearance of female secondary sex characteristics
• Growth of the mammary duct system and numerous other phenomena which vary somewhat in
different species.
Chemistry
The naturally occurring estrogens in humans are:
• β-Estradiol
• Estrone and
• Estriol
The principal estrogenic hormone in circulation and the most active form of the estrogen is β-estradiol.
Normal levels for estradiol are: 30 to 400 pg/mL for premenopausal women. 0 to 30 pg/mL for
postmenopausal women.
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Essential Features:
• Aromatic character of ring A (three double bonds)
• Absence of –CH3 group at C10
• OH GR at C3 possesses the properties of a phenolic –OH group (weakly acid) .
*All naturally occurring estrogens are C18 steroids.
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Androgens are hormones capable of producing certain characteristic masculinizing effects, i.e they
maintain the normal structure and function of the prostate and seminal vesicles and influence the
development of secondary male sex characteristics, such as hair distribution and voice.
Chemistry: The naturally occurring androgens in man are:
1. Testosterone
2. Epiandrosterone (3 β-androsterone)
3. Androsterone and
4. Dehydroepiandrosterone (DHEA).
GONADAL HORMONES
ANDROGENS
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PROGESTATIONAL HORMONES: (LUTEAL HORMONES)
Progesterone is the hormone of the corpus luteum, the structure which develops in the ovary from the
ruptured graafian follicle.
It is also formed by the placenta, which secretes progesterone, during the later part of pregnancy.
Progesterone is also formed in the adrenal cortex, as a precursor of both C19 and C21 corticosteroids.
It is also formed in the testes.
Chemistry:
Progesterone may be regarded as a derivative of “pregnane” and is designated chemically as “4-
pregnane-3, 20-dione”.
It is a C21 steroid and has a – CH3 group at C10 and C13