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HORMONES
INTRODUCTION
Hormones are chemical messengers secreted into blood by
endocrine or ductless glands.
The term hormone was introduced by Satrling in 1905 and
comes from the Greek word “Hormacin” meaning “excite” or
“arouse”.
Hormones are substances synthesized in the body in small
quantities but have a profound biochemical effect in the control
and regulation of metabolic events and contribute in some
cases to intercellular and intracellular communication.
INTRODUCTION
A characteristic of hormones is that they are released, usually
by specialized secretory cells in endocrine glands, and are
carried by the circulation, to target cells where they have an
effect.
INTRODUCTION
The major hormone secreting
glands are:
Pituitary
Thyroid & Parathyroid
Adrenal
Pancreas
Ovaries
Testes
INTRODUCTION
Functions of hormones cover four major areas namely:
a. Reproduction,
b. Growth and development,
c. Maintenance of internal environment, and
d. Energy production, utilization and storage.
CLASSIFICATION OF
HORMONES
Hormones can be classified in several ways, according to:
1. Chemical Composition
2. Location of Receptors
3. Solubility Properties
CLASSIFICATION OF
HORMONES
1. Classification on the Basis of their Chemical
Composition
Hormones can be classified chemically into three major groups.
i. Steroids Hormones: These hormones are fat soluble
compounds like adrenal cortical hormone and sex hormones
(androgens and estrogens).
ii. Amines: these hormones are small, water-soluble
compounds containing amino groups like epinephrine,
thyroxine and several derivatives of tyrosine.
iii. Peptides/Protein Hormones: these are either large protein
or small or medium size peptides e.g., insulin, glucagon and
pituitary hormones.
CLASSIFICATION OF
HORMONES
2. Classification on the Basis of their Mechanism
On this basis, hormones can be classified into two categories.
i. Hormones that bind to Intracellular Receptors: These
include androgens, calcitrol, estrogens, glucocorticoids,
mineralocorticoids, progestins, reticnoic acid, and thyroid
hormones (T3 and T4).
ii. Hormones that bind to Cell Surface Receptors: These
can be further classified on the basis of secondary
messengers. It can be cAMP, cGMP, DAG, InsP3 and
CLASSIFICATION OF
HORMONES
3. Classification on the Basis of Solubility
On the basis of solubility, hormones can be classified as:
i. Lipid-Soluble Hormones: The lipid soluble hormones
include steroid and thyroid hormones.
ii. Water-Soluble Hormones: The water soluble hormones
include amines, peptide hormones, and the eicosanoid
hormones.
CHEMISTRY OF
HORMONES
STEROID HORMONES
These include the sex hormones and the hormones from adrenal
cortex.
These are synthesized in mammals by the ovary (or testis), adrenal
cortex, corpus luteum and the placenta.
Sex Hormones
Three types of sex hormones are recognized :
a. Estrogens (female or ovarian or follicular hormones)
b. Androgens (male or testicular hormones)
c. Progestins (corpus luteal hormones).
STEROID HORMONES
1. Ovarian Hormones
Mammalian ovary contains
ovarian follicles and corpus
lutea.
Hormones produced mainly
the follicles are known as
estrogens.
Chemically, the estrogens
derivatives of a C18
hydrocarbon, estrane.
STEROID HORMONES
The three compounds of this
group with hormonal activity are :
1. β-estradiol
2. Estriol
3. Estrone
STEROID HORMONES
STEROID HORMONES
All these are characterized by the absence of a CH3 group at carbon
10 and by the aromatic nature of ring A, making the OH group
phenolic in character.
Of all these, b-estradiol is most potent physiologically, estrone less
potent and estriol is least active.
Their relative potencies are 50 : 5 : 1 respectively.
Although ovary is the chief source of estrogens, they are in smaller
amounts also produced by the testis and the adrenal cortex.
STEROID HORMONES
2. Testicular
Hormones
These hormones are secreted
mainly by the testes, the male
reproductive organs and are
called as androgens.
Chemically, these are
of a C19 hydrocarbon,
androstane.
They have no side chain on
17-carbon of steroid skeleton.
STEROID HORMONES
There are many hormones
secreted from testes with
androgenic activity.
The three important ones are :
1. Testosterone
2. Androsterone
3. Dehydroepiandrosterone
STEROID HORMONES
Testosterone is most potent of all
these and
dehydroepiandrosterone is least
active.
The relative potency ratio of
these three forms is 20 : 7 : 1.
A few testicular hormones are
also produced by the adrenal
gland.
STEROID HORMONES
3. Corpus Luteal
Hormones
The hormones secreted by the
ovarian bed, corpus luteum are
collectively called as gestagens
progestins.
The principal gestogen is
progesterone.
Progesterone is a C21 steroid
secreted by the corpus luteum
during the second half of the
menstrual cycle.
STEROID HORMONES
4. Adrenal Cortical Hormones
Adrenal cortex secretes some 40-50 closely related C21
collectively called as corticosteroids.
The corticosteroids may be grouped under two categories :
A. Mineralocorticoids. — concerned primarily with the
electrolytes and the distribution of water in tissues, e.g.,
aldosterone and deoxycorticosterone.
B. Glucocorticoids. — concerned primarily with the
carbohydrates, proteins and fats, e.g., cortisone, cortisol
corticosterone.
STEROID HORMONES
STEROID HORMONES
STEROID HORMONES
The estimated 24-hour production of major compounds of human
adrenal gland is :
Corticosteroids
Cortisol 8-24 mg
Corticosterone 1.5−4 mg
Aldosterone 0.04−0.2 mg
STEROID HORMONES
Aldosterone is 30 times more active than deoxycorticosterone.
Deoxycorticosterone, in its turn, is 4 times more potent than cortisone
and cortisol in maintenance of life.
Corticosterone is least active in this regard.
STEROID HORMONES
Classes of Steroid Hormones
Steroid Class Principal Active
Steroid in Humans
No. of Carbon
Atoms
Parent Ring
Structure
Estrogens Estradiol 18 Estrane
Androgens Testosterone 19 Androstane
Progestins Progesterone 21 Pregnane
Glucocorticoids Cortisol 21 Pregnane
Mineralocorticoi
ds
Aldosterone 21 Pregnane
STEROID HORMONES
Biosynthesis of Androgens and Estrogens
 The androgens are synthesized from cholesterol by the
tissues, chiefly from testes.
 In the testes, cholesterol is converted to pregnenolone,
and 17a-hydroxyprogesterone.
 17a-hydroxyprogesterone is then converted to
which is then converted to testosterone and androsterone.
 Testosterone can be converted to estradiol by the action of
aromatase.
 Testosterone can also be converted to dihydrotestosterone by
reductase.
Biosynthesis of Progesterone
 In the corpus luteum, placenta and adrenal cortex,
synthesized from pregnenolone by 3b-hydroxysteroid
 Progesterone is an intermediate common to the biosynthesis
steroid hormone from cholesterol.
STEROID HORMONES
Biosynthesis of Glucocorticoids
 Progesterone is converted to either 17a-hydroxyprogesterone
17a-hydroxylase or to 11-deoxycorticosterone by 21a-
 17a-Hydroxyprogesterone is then converted to 11-
21a-hydroxylase.
 11-deoxycortisol is then converted by 11b-hydroxylase to
 11-deoxycorticosterone is converted to corticosterone by 11b-
hydroxylase.
STEROID HORMONES
Synthesis of Mineralocorticoids
 Corticosterone is converted to aldosterone by 18-hydroxylase.
This reaction is stimulated by angiotensin II, a hormone
angiotensin by angiotensin-converting enzyme.
PEPTIDE HORMONES
Peptide hormones are most prevalent and consist of chains of amino
acids.
Larger peptides are usually referred to as proteins, while complex
protein hormones with carbohydrate side chains are called
glycoprotein hormones.
Peptide Hormones are classified as:
1. Hormones of the pancreas
2. Hormones of the Hypophysis
3. Hormones of the Parathyroid
4. Hormones of the Gastrointestinal Tract
5. Hormones of the Corpus Luteum
PEPTIDE HORMONES
1. Hormones of the Pancreas
Each pancreas has about 1,00,000 islets of Langerhans, which
clusters of various types of cells.
These islets in mammals contain at least 4 major types of cells:
a. α cells
b. β cells
c. δ cells
d. F cells
PEPTIDE HORMONES
The β cells contain granules which manufacture a hormone insulin,
store it and eventually release it directly into the bloodstream at the
appropriate times.
The α cells contain granules which produce another hormone,
glucagon.
The δ cells secrete a hormone, somatostatin.
The F cells secrete pancreatic polypeptide.
The α and β cells make up 20% and 75% of the total, respectively.
PEPTIDE HORMONES
Insulin
Human insulin is a molecule of 5,734 Da which falls on the
between a large polypeptide and a small protein.
It is composed of two separate peptide chains, designated the
and the B chain.
These two chains are joined together by two disulfide bridges.
The human insulin A chain consists of 21 amino acid residues
B chain of 30 amino acid residues.
A third disulfide exists in the A-chain between the cysteine 6
PEPTIDE HORMONES
Amino acid sequence of the A-chain and B-chain of one insulin
molecule.
Biosynthesis of Insulin
 Insulin is synthesized as a pre-prohormone, that is a pre-
proinsulin.
 The initial portion of 23 amino acids is called the leader
sequence and directs the synthesis of pro-insulin. The leader
sequence is cleaved off.
 The pro-insulin which is synthesized has the conformation
necessary for forming the proper disulphide bridges between
A- and B-chains.
 It undergoes a series of site-specific cleavages forming the
mature insulin and an equimolecular amount of connecting
PEPTIDE HORMONES
Glucagon
Glucagon has a molecular weight of 3,485 Da and is comprised
of a single amino acid chain of 29 amino acids that is devoid of
disulfide linkages.
Histidine is the N-terminal amino acid and threonine, the C-
terminal amino acid.
PEPTIDE HORMONES
Glucagon’s N-terminal histidine at position #1 is essential for its
biological activity.
The adjacent residues, #2 (serine) and #5 (threonine), are involved in
implementing the adenylyl cyclase activity which is key to the
initiation of glucagon-mediated biological responses.
Residues #19–#26 (blue color) have an equal potential to stabilize the
structure either as β sheets, or as α-helices.
The C-terminal two residues, asparagine (#28) and threonine (#29),
increase glucagon’s tight binding to its receptor.
Unlike insulin, it contains no cystine, proline or isoleucine, but
possesses methionine and tryptophan in appreciable amounts.
PEPTIDE HORMONES
PEPTIDE HORMONES
Somatostatin
Two forms of somatostatin exists; S14 and S28, which are
single chain polypeptides of 14 and 28 amino acids,
respectively.
Somatostatin-14 has one disulfide bond.
It is produced by the δ-cells of the endocrine pancreas and
dispersed cells in the gastrointestinal tract.
PEPTIDE HORMONES
Other Pancreatic Hormones
A. Pancreatic Polypeptide (PP)
Pancreatic polypeptide (PP) is a 36-amino-acid peptide that is
known to stimulate the gastric secretion of HCl and pepsin.
Most of the PP is expressed and then secreted by the F cells of
the pancreas.
PP circulates in the plasma as a dimer with a half-life of 6–7
minutes.
PEPTIDE HORMONES
B. Amylin
The pancreatic β-cell islets produce the peptide hormone
amylin.
It has also been formerly known as islet amyloid polypeptide
(IAPP).
Amylin is a 37-amino-acid peptide.
Amylin and insulin are co-secreted from the pancreatic beta
cells at the time of food intake.
PEPTIDE HORMONES
Constituent Hormones of Endocrine Pancreas
Cell Type Hormone Structure
a Glucagon 29 amino acids
b
Insulin
Amylin
Two chains:
a= 21 amino acids
b = 30 amino acids
37 amino acids
d
Somatostatin Two forms:
S-14 = 14 amino
acids
S-28 = 28 amino
acids
F Pancreatic Polypeptide 36 amino acids
PEPTIDE HORMONES
2. Hormones of the Hypophysis or Pituitary
Gland
Hypophysis or pituitary gland consists of 3 lobes:
a) An anterior lobe or adenohypophysis
b) An intermediate lobe
c) A posterior lobe or neurohypophysis
All the three lobes secrete substances having hormonal activity.
PEPTIDE HORMONES
The secretion of pituitary hormones is controlled by the hormones (or factors)
released from hypothalamus, a region of the brain immediately proximal to the
pituitary.
These hormones are called as hypothalamo-releasing hormones or
hypothalamic factors.
Sr. no. Pituitary Hormones Hypothalmic Releasing Hormone
1 Thyroid Stimulating Hormone, TSH Thyrotrophin Releasing Hormone, TRH
2 Adrenocorticotrophic Hormone,
ACTH
Corticotrophin releasing Hormone, CRH
3 Follicle Stimulating Hormone, FSH
Luteinizing Hormone, LH
Gonadotrophin releasing Hormone, GnRH
4 Growth Hormone, GH Growth Hormone Releasing Hormone,
GHRH
5 Prolactin, PL Prolactin releasing Hormone, PLRH
PEPTIDE HORMONES
a) Hormones of Anterior Pituitary (Adenohypophysis)
Anterior pituitary gland (Adenohypophysis) secrete a number of
hormones of vital importance and all of them are protein in nature, and
these nourish the secretory activities of other glands.
These hormones are called as tropins or trophic hormones.
PEPTIDE HORMONES
A. Thyrotropin or Thyroid-Stimulating Hormone, TSH.
The molecule of TSH is a dimer made up of a and b subunits.
It is a glycoprotein with molecular weight about 30,000.
Each molecule has 8-9 cystine residues and the disulfide
present as intrachain linkages rather than interchain linkages.
PEPTIDE HORMONES
B. Corticotropin or Adrenocorticotrophic Hormone, ACTH.
Corticotropin is a straight chain polypeptide with a molecular
about 4,500 and consists of 39 amino acid residues.
The most potent segment of activity is from residue 15 to 18
(Lys.Lys.Arg. Arg).
The release of ACTH is controlled by CRH.
PEPTIDE HORMONES
C. Gonadotropins or Gonadotrophic Hormones, GTH.
Gonadotropins include:
i. Follicle Stimulating Hormone, FSH
ii. Luteinizing hormone, LH
iii. Prolactin, PRL
The gonadotropins, FSH and LH, are both regulated by the
hypothalamic gonadotrophin releasing hormone, GnRH.
PEPTIDE HORMONES
i. Follicle-stimulating hormone, FSH
 It is a glycoprotein that contains galactose, mannose,
galactosamine, glucosamine, sialic acid, fucose and uronic acid.
 It has a molecular weight of about 30,000 in man.
ii. Luteinizing hormone, LH
 It is a peptide hormone with molecular weight of about 26,000 (in
man).
 It lacks tryptophan but has a high content of cystine and proline.
 Each molecule contains 10 glucosamine and 3 galactosamine
residues.
PEPTIDE HORMONES
iii. Prolactin PRL, Luteotrophic Hormone, LTH
This is also a peptide hormone with 198 amino acid residues and a
molecular weight of about 23,500.
It has 3 disulfide bonds between cysteine residues at 4-11, 58-173
and 190-198.
It differs from FSH and LH in that it contains no carbohydrate.
PEPTIDE HORMONES
Prolactin.
PEPTIDE HORMONES
D. Somatotropin or Somatotrophic hormone, STH or Growth
Hormone, GH.
Somatotropin obtained from human hypophysis is a protein
with molecular weight 27,000.
It has 191 amino acids and consists of 2 disulfide bridges
between adjacent cysteine residues.
The N-terminal and C-terminal residues are both
phenylalanine.
PEPTIDE HORMONES
Constituent Hormones of Anterior Pituitary (Adenohypophysis)
Cell Type Hormone Structure
Basophils or β cells
Thyrotropin, TSH Two Protein Subunits:
a = 96 amino acids
b = 112 amino acids
Neutrophils or
chromophobe cells
Corticotropin,
ACTH
Polypeptide = 39 amino
acids
Basophils or β cells
FSH Two Protein Subunits:
a = 96 amino acids
b = 111 amino acids
Basophils or β cells
LH Two Protein Subunits:
a = 96 amino acids
b = 121 amino acids
PEPTIDE HORMONES
Constituent Hormones of Anterior Pituitary (Adenohypophysis)
Cell Type Hormone Structure
Acidophils or α cells
Prolactin, PRL Protein of 198 amino
acids
Acidophils or α cells
Growth Hormone, GH
or Somatotropin, STH
Protein of 191amino
acids
PEPTIDE HORMONES
b) Hormones of Posterior Pituitary or Neurohypophysis
Two important hormones are secreted from the posterior
pituitary in both males and females.
These are:
a. Oxytocin (OT)
b. Vasopressin (VP), the antidiuretic hormone,
The two hormones are structurally closely related nonapeptides
that are derived from a common ancestral gene.
PEPTIDE HORMONES
a. Oxytocin
It is a nonapeptide amide.
A disulfide bond is present to link the two cysteine residues present in
the molecule.
b. Vasopressin
It is also a cyclic nonapeptide amide and resembles oxytocin except
that isoleucine is replaced by phenylalanine and leucine by arginine.
PEPTIDE HORMONES
PEPTIDE HORMONES
Constituent Hormones of Posterior Pituitary (Neurohypophysis)
Hormone Structure
Oxytocin Polypeptide of 9 amino acids
(CYIQNCPLG)
C’s are disulfide bonded
Vasopressin or Antidiuretic Hormone Polypeptide of 9 amino acids
(CYFQNCPRG)
C’s are disulfide bonded
PEPTIDE HORMONES
3. Hormones of the Parathyroid
Parathyroids secrete a hormone called parathyroid hormone
(parathormone, PTH) or Collip’s hormone.
It is a linear polypeptide consisting of 84 amino acids
weight=9300) with no cysteine residues and hence no disulfide
bridges.
A fragment of the intact hormone consisting of the first 34
at the N-terminal region of the molecule is sufficient for the
exert its entire spectrum of characteristic biological effects.
PEPTIDE HORMONES
4. Hormones of the Gastrointestinal Tract
The gastrointestinal hormones are a family of polypeptides
by specialized endocrine cells present in the stomach, intestine,
colon which function both as traditional hormonal messengers
neurotransmitters.
Of the many regulatory gastrointestinal peptides, following are
understood are considered to be the authentic hormones:
A.Gastrin
B. Secretin
C.Cholecystokinin (CCK)
PEPTIDE HORMONES
A. Gastrin
It is produced G cells in the pyloric mucosa, which is apparently
stimulated by the proteins present in food or possibly by HCl.
The main form of gastrin obtained from G cells is a heptadecapeptide.
At the N-terminal end of the heptadecapeptide, there is a pyroglutamyl
residue, and at the c-terminal end, there is a phenylalaninamide
residue.
PEPTIDE HORMONES
Two forms of heptadecapeptide exist:
I. One in which the tyrosyl residue at postion 12 is free (Gastrin 1)
II. The other in which it is sulphated.
PEPTIDE HORMONES
B. Secretin
Secretin has only 27 amino acids with molecular weight of 3,056.
The entire molecule of 27 amino acids is required for full biological
activity.
Secretin is localized to the upper duodenal and jejunal S cells.
PEPTIDE HORMONES
C. Cholycystokinin, CCK
It is also secreted by the upper part of the small intestine.
Cholecystokinin is a polypeptide with 33 amino acid residues and a
molecular weight of 3,883.
It is, however, noteworthy that the last 5 amino acids towards the C-
terminal in the gastrin and cholecystokinin are exactly the same.
It is in this terminal portion of these hormones that the principal
activity resides.
PEPTIDE HORMONES
AMINO ACID DERIVATIVES
1. Thyroidal Hormones
The mammalian thyroid gland biosynthesizes, stores, and
secretes two molecular species of thyroid hormone:
I. Thyroxine (T4; 3,5,3′,5′-tetraiodothyronine)
II. Triiodothyronine (T3; 3,5,3′-triiodothyronine)
AMINO ACID DERIVATIVES
AMINO ACID DERIVATIVES
Thyroid hormones are poorly soluble in water, and more than 99% of
the T3 and T4 circulating in the blood is bound to a carrier proteins.
The principle carrier of thyroid hormones is thyroxin-binding globulin.
AMINO ACID DERIVATIVES
[Calcitonin (CT) is a small polypeptide hormone secreted by the
specialized C cells that are found primarily in the thyroid gland.
It consisting of a straight chain peptide of 32 amino acids, with
a seven-membered disulfide ring at the N-terminus and a
prolinamide residue at the C-terminus. ]
AMINO ACID DERIVATIVES
2. Hormones of Adrenal Medulla
The adrenal medulla produces two hormones:
a. Epinephrine or Adrenaline
b. Norepinephrine or Noradrenaline
Chemically, these two hormones are catecholamines
(dihydroxyphenylamines) and are closely related to tyrosine and
phenylalanine.
Norepinephrine, however, differs from epinephrine structurally
in having a hydrogen atom in place of the methyl group.
AMINO ACID DERIVATIVES

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Hormones

  • 2. INTRODUCTION Hormones are chemical messengers secreted into blood by endocrine or ductless glands. The term hormone was introduced by Satrling in 1905 and comes from the Greek word “Hormacin” meaning “excite” or “arouse”. Hormones are substances synthesized in the body in small quantities but have a profound biochemical effect in the control and regulation of metabolic events and contribute in some cases to intercellular and intracellular communication.
  • 3. INTRODUCTION A characteristic of hormones is that they are released, usually by specialized secretory cells in endocrine glands, and are carried by the circulation, to target cells where they have an effect.
  • 4. INTRODUCTION The major hormone secreting glands are: Pituitary Thyroid & Parathyroid Adrenal Pancreas Ovaries Testes
  • 5. INTRODUCTION Functions of hormones cover four major areas namely: a. Reproduction, b. Growth and development, c. Maintenance of internal environment, and d. Energy production, utilization and storage.
  • 6. CLASSIFICATION OF HORMONES Hormones can be classified in several ways, according to: 1. Chemical Composition 2. Location of Receptors 3. Solubility Properties
  • 7. CLASSIFICATION OF HORMONES 1. Classification on the Basis of their Chemical Composition Hormones can be classified chemically into three major groups. i. Steroids Hormones: These hormones are fat soluble compounds like adrenal cortical hormone and sex hormones (androgens and estrogens). ii. Amines: these hormones are small, water-soluble compounds containing amino groups like epinephrine, thyroxine and several derivatives of tyrosine. iii. Peptides/Protein Hormones: these are either large protein or small or medium size peptides e.g., insulin, glucagon and pituitary hormones.
  • 8. CLASSIFICATION OF HORMONES 2. Classification on the Basis of their Mechanism On this basis, hormones can be classified into two categories. i. Hormones that bind to Intracellular Receptors: These include androgens, calcitrol, estrogens, glucocorticoids, mineralocorticoids, progestins, reticnoic acid, and thyroid hormones (T3 and T4). ii. Hormones that bind to Cell Surface Receptors: These can be further classified on the basis of secondary messengers. It can be cAMP, cGMP, DAG, InsP3 and
  • 9. CLASSIFICATION OF HORMONES 3. Classification on the Basis of Solubility On the basis of solubility, hormones can be classified as: i. Lipid-Soluble Hormones: The lipid soluble hormones include steroid and thyroid hormones. ii. Water-Soluble Hormones: The water soluble hormones include amines, peptide hormones, and the eicosanoid hormones.
  • 11. STEROID HORMONES These include the sex hormones and the hormones from adrenal cortex. These are synthesized in mammals by the ovary (or testis), adrenal cortex, corpus luteum and the placenta. Sex Hormones Three types of sex hormones are recognized : a. Estrogens (female or ovarian or follicular hormones) b. Androgens (male or testicular hormones) c. Progestins (corpus luteal hormones).
  • 12. STEROID HORMONES 1. Ovarian Hormones Mammalian ovary contains ovarian follicles and corpus lutea. Hormones produced mainly the follicles are known as estrogens. Chemically, the estrogens derivatives of a C18 hydrocarbon, estrane.
  • 13. STEROID HORMONES The three compounds of this group with hormonal activity are : 1. β-estradiol 2. Estriol 3. Estrone
  • 15. STEROID HORMONES All these are characterized by the absence of a CH3 group at carbon 10 and by the aromatic nature of ring A, making the OH group phenolic in character. Of all these, b-estradiol is most potent physiologically, estrone less potent and estriol is least active. Their relative potencies are 50 : 5 : 1 respectively. Although ovary is the chief source of estrogens, they are in smaller amounts also produced by the testis and the adrenal cortex.
  • 16. STEROID HORMONES 2. Testicular Hormones These hormones are secreted mainly by the testes, the male reproductive organs and are called as androgens. Chemically, these are of a C19 hydrocarbon, androstane. They have no side chain on 17-carbon of steroid skeleton.
  • 17. STEROID HORMONES There are many hormones secreted from testes with androgenic activity. The three important ones are : 1. Testosterone 2. Androsterone 3. Dehydroepiandrosterone
  • 18. STEROID HORMONES Testosterone is most potent of all these and dehydroepiandrosterone is least active. The relative potency ratio of these three forms is 20 : 7 : 1. A few testicular hormones are also produced by the adrenal gland.
  • 19. STEROID HORMONES 3. Corpus Luteal Hormones The hormones secreted by the ovarian bed, corpus luteum are collectively called as gestagens progestins. The principal gestogen is progesterone. Progesterone is a C21 steroid secreted by the corpus luteum during the second half of the menstrual cycle.
  • 20. STEROID HORMONES 4. Adrenal Cortical Hormones Adrenal cortex secretes some 40-50 closely related C21 collectively called as corticosteroids. The corticosteroids may be grouped under two categories : A. Mineralocorticoids. — concerned primarily with the electrolytes and the distribution of water in tissues, e.g., aldosterone and deoxycorticosterone. B. Glucocorticoids. — concerned primarily with the carbohydrates, proteins and fats, e.g., cortisone, cortisol corticosterone.
  • 23. STEROID HORMONES The estimated 24-hour production of major compounds of human adrenal gland is : Corticosteroids Cortisol 8-24 mg Corticosterone 1.5−4 mg Aldosterone 0.04−0.2 mg
  • 24. STEROID HORMONES Aldosterone is 30 times more active than deoxycorticosterone. Deoxycorticosterone, in its turn, is 4 times more potent than cortisone and cortisol in maintenance of life. Corticosterone is least active in this regard.
  • 25. STEROID HORMONES Classes of Steroid Hormones Steroid Class Principal Active Steroid in Humans No. of Carbon Atoms Parent Ring Structure Estrogens Estradiol 18 Estrane Androgens Testosterone 19 Androstane Progestins Progesterone 21 Pregnane Glucocorticoids Cortisol 21 Pregnane Mineralocorticoi ds Aldosterone 21 Pregnane
  • 27. Biosynthesis of Androgens and Estrogens  The androgens are synthesized from cholesterol by the tissues, chiefly from testes.  In the testes, cholesterol is converted to pregnenolone, and 17a-hydroxyprogesterone.  17a-hydroxyprogesterone is then converted to which is then converted to testosterone and androsterone.  Testosterone can be converted to estradiol by the action of aromatase.  Testosterone can also be converted to dihydrotestosterone by reductase.
  • 28. Biosynthesis of Progesterone  In the corpus luteum, placenta and adrenal cortex, synthesized from pregnenolone by 3b-hydroxysteroid  Progesterone is an intermediate common to the biosynthesis steroid hormone from cholesterol.
  • 29. STEROID HORMONES Biosynthesis of Glucocorticoids  Progesterone is converted to either 17a-hydroxyprogesterone 17a-hydroxylase or to 11-deoxycorticosterone by 21a-  17a-Hydroxyprogesterone is then converted to 11- 21a-hydroxylase.  11-deoxycortisol is then converted by 11b-hydroxylase to  11-deoxycorticosterone is converted to corticosterone by 11b- hydroxylase.
  • 30. STEROID HORMONES Synthesis of Mineralocorticoids  Corticosterone is converted to aldosterone by 18-hydroxylase. This reaction is stimulated by angiotensin II, a hormone angiotensin by angiotensin-converting enzyme.
  • 31. PEPTIDE HORMONES Peptide hormones are most prevalent and consist of chains of amino acids. Larger peptides are usually referred to as proteins, while complex protein hormones with carbohydrate side chains are called glycoprotein hormones. Peptide Hormones are classified as: 1. Hormones of the pancreas 2. Hormones of the Hypophysis 3. Hormones of the Parathyroid 4. Hormones of the Gastrointestinal Tract 5. Hormones of the Corpus Luteum
  • 32. PEPTIDE HORMONES 1. Hormones of the Pancreas Each pancreas has about 1,00,000 islets of Langerhans, which clusters of various types of cells. These islets in mammals contain at least 4 major types of cells: a. α cells b. β cells c. δ cells d. F cells
  • 33. PEPTIDE HORMONES The β cells contain granules which manufacture a hormone insulin, store it and eventually release it directly into the bloodstream at the appropriate times. The α cells contain granules which produce another hormone, glucagon. The δ cells secrete a hormone, somatostatin. The F cells secrete pancreatic polypeptide. The α and β cells make up 20% and 75% of the total, respectively.
  • 34. PEPTIDE HORMONES Insulin Human insulin is a molecule of 5,734 Da which falls on the between a large polypeptide and a small protein. It is composed of two separate peptide chains, designated the and the B chain. These two chains are joined together by two disulfide bridges. The human insulin A chain consists of 21 amino acid residues B chain of 30 amino acid residues. A third disulfide exists in the A-chain between the cysteine 6
  • 35. PEPTIDE HORMONES Amino acid sequence of the A-chain and B-chain of one insulin molecule.
  • 36. Biosynthesis of Insulin  Insulin is synthesized as a pre-prohormone, that is a pre- proinsulin.  The initial portion of 23 amino acids is called the leader sequence and directs the synthesis of pro-insulin. The leader sequence is cleaved off.  The pro-insulin which is synthesized has the conformation necessary for forming the proper disulphide bridges between A- and B-chains.  It undergoes a series of site-specific cleavages forming the mature insulin and an equimolecular amount of connecting
  • 37. PEPTIDE HORMONES Glucagon Glucagon has a molecular weight of 3,485 Da and is comprised of a single amino acid chain of 29 amino acids that is devoid of disulfide linkages. Histidine is the N-terminal amino acid and threonine, the C- terminal amino acid.
  • 38. PEPTIDE HORMONES Glucagon’s N-terminal histidine at position #1 is essential for its biological activity. The adjacent residues, #2 (serine) and #5 (threonine), are involved in implementing the adenylyl cyclase activity which is key to the initiation of glucagon-mediated biological responses. Residues #19–#26 (blue color) have an equal potential to stabilize the structure either as β sheets, or as α-helices. The C-terminal two residues, asparagine (#28) and threonine (#29), increase glucagon’s tight binding to its receptor. Unlike insulin, it contains no cystine, proline or isoleucine, but possesses methionine and tryptophan in appreciable amounts.
  • 40. PEPTIDE HORMONES Somatostatin Two forms of somatostatin exists; S14 and S28, which are single chain polypeptides of 14 and 28 amino acids, respectively. Somatostatin-14 has one disulfide bond. It is produced by the δ-cells of the endocrine pancreas and dispersed cells in the gastrointestinal tract.
  • 41. PEPTIDE HORMONES Other Pancreatic Hormones A. Pancreatic Polypeptide (PP) Pancreatic polypeptide (PP) is a 36-amino-acid peptide that is known to stimulate the gastric secretion of HCl and pepsin. Most of the PP is expressed and then secreted by the F cells of the pancreas. PP circulates in the plasma as a dimer with a half-life of 6–7 minutes.
  • 42. PEPTIDE HORMONES B. Amylin The pancreatic β-cell islets produce the peptide hormone amylin. It has also been formerly known as islet amyloid polypeptide (IAPP). Amylin is a 37-amino-acid peptide. Amylin and insulin are co-secreted from the pancreatic beta cells at the time of food intake.
  • 43. PEPTIDE HORMONES Constituent Hormones of Endocrine Pancreas Cell Type Hormone Structure a Glucagon 29 amino acids b Insulin Amylin Two chains: a= 21 amino acids b = 30 amino acids 37 amino acids d Somatostatin Two forms: S-14 = 14 amino acids S-28 = 28 amino acids F Pancreatic Polypeptide 36 amino acids
  • 44. PEPTIDE HORMONES 2. Hormones of the Hypophysis or Pituitary Gland Hypophysis or pituitary gland consists of 3 lobes: a) An anterior lobe or adenohypophysis b) An intermediate lobe c) A posterior lobe or neurohypophysis All the three lobes secrete substances having hormonal activity.
  • 45. PEPTIDE HORMONES The secretion of pituitary hormones is controlled by the hormones (or factors) released from hypothalamus, a region of the brain immediately proximal to the pituitary. These hormones are called as hypothalamo-releasing hormones or hypothalamic factors. Sr. no. Pituitary Hormones Hypothalmic Releasing Hormone 1 Thyroid Stimulating Hormone, TSH Thyrotrophin Releasing Hormone, TRH 2 Adrenocorticotrophic Hormone, ACTH Corticotrophin releasing Hormone, CRH 3 Follicle Stimulating Hormone, FSH Luteinizing Hormone, LH Gonadotrophin releasing Hormone, GnRH 4 Growth Hormone, GH Growth Hormone Releasing Hormone, GHRH 5 Prolactin, PL Prolactin releasing Hormone, PLRH
  • 46. PEPTIDE HORMONES a) Hormones of Anterior Pituitary (Adenohypophysis) Anterior pituitary gland (Adenohypophysis) secrete a number of hormones of vital importance and all of them are protein in nature, and these nourish the secretory activities of other glands. These hormones are called as tropins or trophic hormones.
  • 47. PEPTIDE HORMONES A. Thyrotropin or Thyroid-Stimulating Hormone, TSH. The molecule of TSH is a dimer made up of a and b subunits. It is a glycoprotein with molecular weight about 30,000. Each molecule has 8-9 cystine residues and the disulfide present as intrachain linkages rather than interchain linkages.
  • 48. PEPTIDE HORMONES B. Corticotropin or Adrenocorticotrophic Hormone, ACTH. Corticotropin is a straight chain polypeptide with a molecular about 4,500 and consists of 39 amino acid residues. The most potent segment of activity is from residue 15 to 18 (Lys.Lys.Arg. Arg). The release of ACTH is controlled by CRH.
  • 49. PEPTIDE HORMONES C. Gonadotropins or Gonadotrophic Hormones, GTH. Gonadotropins include: i. Follicle Stimulating Hormone, FSH ii. Luteinizing hormone, LH iii. Prolactin, PRL The gonadotropins, FSH and LH, are both regulated by the hypothalamic gonadotrophin releasing hormone, GnRH.
  • 50. PEPTIDE HORMONES i. Follicle-stimulating hormone, FSH  It is a glycoprotein that contains galactose, mannose, galactosamine, glucosamine, sialic acid, fucose and uronic acid.  It has a molecular weight of about 30,000 in man. ii. Luteinizing hormone, LH  It is a peptide hormone with molecular weight of about 26,000 (in man).  It lacks tryptophan but has a high content of cystine and proline.  Each molecule contains 10 glucosamine and 3 galactosamine residues.
  • 51. PEPTIDE HORMONES iii. Prolactin PRL, Luteotrophic Hormone, LTH This is also a peptide hormone with 198 amino acid residues and a molecular weight of about 23,500. It has 3 disulfide bonds between cysteine residues at 4-11, 58-173 and 190-198. It differs from FSH and LH in that it contains no carbohydrate.
  • 53. PEPTIDE HORMONES D. Somatotropin or Somatotrophic hormone, STH or Growth Hormone, GH. Somatotropin obtained from human hypophysis is a protein with molecular weight 27,000. It has 191 amino acids and consists of 2 disulfide bridges between adjacent cysteine residues. The N-terminal and C-terminal residues are both phenylalanine.
  • 54. PEPTIDE HORMONES Constituent Hormones of Anterior Pituitary (Adenohypophysis) Cell Type Hormone Structure Basophils or β cells Thyrotropin, TSH Two Protein Subunits: a = 96 amino acids b = 112 amino acids Neutrophils or chromophobe cells Corticotropin, ACTH Polypeptide = 39 amino acids Basophils or β cells FSH Two Protein Subunits: a = 96 amino acids b = 111 amino acids Basophils or β cells LH Two Protein Subunits: a = 96 amino acids b = 121 amino acids
  • 55. PEPTIDE HORMONES Constituent Hormones of Anterior Pituitary (Adenohypophysis) Cell Type Hormone Structure Acidophils or α cells Prolactin, PRL Protein of 198 amino acids Acidophils or α cells Growth Hormone, GH or Somatotropin, STH Protein of 191amino acids
  • 56. PEPTIDE HORMONES b) Hormones of Posterior Pituitary or Neurohypophysis Two important hormones are secreted from the posterior pituitary in both males and females. These are: a. Oxytocin (OT) b. Vasopressin (VP), the antidiuretic hormone, The two hormones are structurally closely related nonapeptides that are derived from a common ancestral gene.
  • 57. PEPTIDE HORMONES a. Oxytocin It is a nonapeptide amide. A disulfide bond is present to link the two cysteine residues present in the molecule. b. Vasopressin It is also a cyclic nonapeptide amide and resembles oxytocin except that isoleucine is replaced by phenylalanine and leucine by arginine.
  • 59. PEPTIDE HORMONES Constituent Hormones of Posterior Pituitary (Neurohypophysis) Hormone Structure Oxytocin Polypeptide of 9 amino acids (CYIQNCPLG) C’s are disulfide bonded Vasopressin or Antidiuretic Hormone Polypeptide of 9 amino acids (CYFQNCPRG) C’s are disulfide bonded
  • 60. PEPTIDE HORMONES 3. Hormones of the Parathyroid Parathyroids secrete a hormone called parathyroid hormone (parathormone, PTH) or Collip’s hormone. It is a linear polypeptide consisting of 84 amino acids weight=9300) with no cysteine residues and hence no disulfide bridges. A fragment of the intact hormone consisting of the first 34 at the N-terminal region of the molecule is sufficient for the exert its entire spectrum of characteristic biological effects.
  • 61. PEPTIDE HORMONES 4. Hormones of the Gastrointestinal Tract The gastrointestinal hormones are a family of polypeptides by specialized endocrine cells present in the stomach, intestine, colon which function both as traditional hormonal messengers neurotransmitters. Of the many regulatory gastrointestinal peptides, following are understood are considered to be the authentic hormones: A.Gastrin B. Secretin C.Cholecystokinin (CCK)
  • 62. PEPTIDE HORMONES A. Gastrin It is produced G cells in the pyloric mucosa, which is apparently stimulated by the proteins present in food or possibly by HCl. The main form of gastrin obtained from G cells is a heptadecapeptide. At the N-terminal end of the heptadecapeptide, there is a pyroglutamyl residue, and at the c-terminal end, there is a phenylalaninamide residue.
  • 63. PEPTIDE HORMONES Two forms of heptadecapeptide exist: I. One in which the tyrosyl residue at postion 12 is free (Gastrin 1) II. The other in which it is sulphated.
  • 64. PEPTIDE HORMONES B. Secretin Secretin has only 27 amino acids with molecular weight of 3,056. The entire molecule of 27 amino acids is required for full biological activity. Secretin is localized to the upper duodenal and jejunal S cells.
  • 65. PEPTIDE HORMONES C. Cholycystokinin, CCK It is also secreted by the upper part of the small intestine. Cholecystokinin is a polypeptide with 33 amino acid residues and a molecular weight of 3,883. It is, however, noteworthy that the last 5 amino acids towards the C- terminal in the gastrin and cholecystokinin are exactly the same. It is in this terminal portion of these hormones that the principal activity resides.
  • 67. AMINO ACID DERIVATIVES 1. Thyroidal Hormones The mammalian thyroid gland biosynthesizes, stores, and secretes two molecular species of thyroid hormone: I. Thyroxine (T4; 3,5,3′,5′-tetraiodothyronine) II. Triiodothyronine (T3; 3,5,3′-triiodothyronine)
  • 69. AMINO ACID DERIVATIVES Thyroid hormones are poorly soluble in water, and more than 99% of the T3 and T4 circulating in the blood is bound to a carrier proteins. The principle carrier of thyroid hormones is thyroxin-binding globulin.
  • 70. AMINO ACID DERIVATIVES [Calcitonin (CT) is a small polypeptide hormone secreted by the specialized C cells that are found primarily in the thyroid gland. It consisting of a straight chain peptide of 32 amino acids, with a seven-membered disulfide ring at the N-terminus and a prolinamide residue at the C-terminus. ]
  • 71. AMINO ACID DERIVATIVES 2. Hormones of Adrenal Medulla The adrenal medulla produces two hormones: a. Epinephrine or Adrenaline b. Norepinephrine or Noradrenaline Chemically, these two hormones are catecholamines (dihydroxyphenylamines) and are closely related to tyrosine and phenylalanine. Norepinephrine, however, differs from epinephrine structurally in having a hydrogen atom in place of the methyl group.