HORMONE

Hormone is a chemical messenger, secreted in trace amount by specific

cells that carries a signal to generate some alternation at the cellular level

The endocrine (or) ductless glands secrete hormones directly into the blood
stream

Systemic or general hormones

Hormones act on distant targets ( via the blood stream )

Local hormones
Local hormones act mainly in the tissues and sites in which they are
produced eg. Eicosanoids, endothelin, nitric oxide, histamine etc
Tropic hormones

Stimulate the secretion of hormones from other endocrine glands or tissues

They also promote the synthesis of hormones and increase the vascularity
and the growth of the target gland or tissue

Endocrine hormone

That arise in one tissue, or gland and travel a considerable distance

through the circulation to reach a target cell

Paracrine hormone

Arise from a cell and travel a relatively small distance

Autocrine hormone

Are produced by the cells that are also a target cell

GENERAL CHARACTERISTICS OF HORMONE

1. Chemical nature of hormone
2. Types of synthesis and modification of hormones
3. Transport of hormones
4. Concentration of hormones in body fluids
5. Feedback control of plasma hormone level
6. Target cell
7. receptors
1.Chemical nature of hormone

lipid derivatives

Steroids: --------

adrenocortical hormone, sex hormones and 1.25 DHCC

Fatty acid-------

prostaglandin

Retinols---------

retinoic acid

 Protein and amino acid derivatives

Proteins -----------------Insulin, growth hormone, parathyroid hormone, prolactin,
chorionic somatotrophin
Peptides------------------antidiuretic hormone, glucagon and adrenocorticotropic
hormone, melanocyte stimulating hormone, endorphins, oxytocin, thyrotrophin
releasing hormone
Glycoprotein-------------thyroid stimulating hormone, follicular stimulating
hormone, leutinizing hormone and human chorionic gonadotrophin
Amino acid (tyrosine) derivatives----------(T3, T4)

catecholamine and thyroid hormones

2.Types of synthesis and modification of hormones

1. Hormones synthesized and secreted as active form
estriol, aldosterone, cortisol, catecholamines
2. Hormones that are modified in the secreting cells prior to secretion
parathyroid hormone , insulin, pro-opiomelanocortin
3. Hormones that are converted to active form in the peripheral tissue
Target tissue
--------dihydrotestosterone
Non-target tissue --------

T4 to T3 in liver and pituitary , testosterone to

DHEA to testosterone

Combination of target and non- target tissue -------------- Vitamin D to 1, 25 DHCC

3. Transportation of hormones
Hormones can be transported as free form or bound form
Lipid soluble hormones in plasma are bound to protein. T 3 and T4 bound to
thyroxine binding globulin (TBG) and thyroxine binding prealbumin (TBPA),
Glucocorticoids are bound to a globulin (transcortin) or corticoticosteroid binding
globulin (CBG) or albumin.
Only the free or unbound hormone have biologic activities. Hormones
bound to proteins cannot be destroyed and therefore their half-life is long
4. Interactions of hormone
tissue

Inhibitory interaction --------2 hormones have opposite effects on target

eg. Growth hormone and insulin

Synergistic interaction-------2 hormones administered simultaneously give
an effect greater than the sum of either of them given alone
eg. FSH and LH on follicular growth, LH alone has no effect on follicular growth
Permissive interaction
A small quantity of one hormone allows full response to another hormone
5.Concentration of Hormones in the body fluid
Hormones are present at very low concentration in the ECF ( 10-15 to 10-9
mol/L)
6. Feedback control of plasma hormone level

When circulating hormone level is increased, the hormone can control its
synthesis by negative feedback regulation When circulating hormone level is
decreased, the hormone can control its synthesis by positive feed forward
regulation

7.Target cell
It is the type of cell that able to recognize specific hormone due to
presence of specific receptor
Target cells must distinguish not only between different hormones but also
between a given hormone and related molecules
8. Receptors
Receptors are proteins that bind a specific extracellular signaling molecule
(ligand) and initiate a response in the cell. They are located on the cell
surface or in the cytosol/ nucleus of the target cell

Receptors have very high specificity and affinity to its hormone. Hormone
receptors are protein in nature

All receptors whether for polypeptide or steroid hormones have at least 2

functional domains

1. a recognition domain binds the hormones

2. a second region generates a signal that couples hormone recognition to some
intracellular function

RECEPTORS
The action of hormone starts by binding to cell associated recognition molecule
called receptors. Receptors are proteins that bind a specific extracellular signal
molecule (ligand) and initiates a response in the cell. They are protein or glycoprotein in
nature. There are 2 types of receptors
1. Intracellular receptors
2. Cell surface receptors.
1) Intracellular receptors
Receptors for lipophilic (steroid) hormones are present in the cytosol or nucleus
of target cells. Their action is by mediating gene expression. Steroid hormone receptors
have several functional domains--1.
2.
3.
4.
5.

Hormone binding domain

Adjacent DNA binding domain
Site that bind to specific DNA region
Site that activate or repress gene expression
Site for translocation of receptor from cytoplasm to nucleus.

2) Cell surface receptors

Receptors for hydrophilic hormones are present on cell surface and their actions
are mediated by second messengers. These cell surface receptors act as signal

transducer and generates signals that alter the behavior of target cell. Cell surface
receptors have 3 functional domains--1. Hormone binding domain
2. Transmembrane domain
3. Signal transduction domain

Most cell surface receptors belong to one of the three classes. They are
1. Ion-channeled linked receptors
2. G-protein linked receptors
3. Enzyme linked receptors
(1) Ion-channeled linked receptors
Also known as transmitter gated ion channels.
These receptors are concentrated in post synaptic cell membrane.
Neurotransmitters transiently open or close the ion channel and alter the
permeability of cell membrane.
They belong to homologous multi-pass trans-membrane proteins.
E.g, receptor for acetylcholine
(2)G-protein linked receptors
They act indirectly to regulate the activity of separate membrane bound target
protein which can be an enzyme or ion channel.
The interaction between the receptor and target protein is mediated by G-protein.
They belong to homologous seven pass trans-membrane protein.
Example receptors for catecholamine
(3)Enzyme linked receptors
These receptors either function as enzymes or associated with enzymes.
They are heterogenous single pass trans-membrane protein.
Example , receptor for insulin
The number of receptors in cells are not static , they are dynamic in nature. When
the hormone is present in excess, the number of active receptor is decreased by
internalization, desensitization and repression(down regulation). If the amount of
hormone is decreased, the number of receptor will increase by induction(up regulation)
Biomedical importance.
Androgen receptor agonist enhances the development of lean muscle mass.
Estrogen receptor antagonists (tamoxifen) are used in treatment of breast cancer.

CLASSIFICATION OF HORMONES BY THE MECHANISM OF ACTION

1. Hormones that bind to intracellular receptor

Androgens, estrogens, progestins

Calcitriol (1,25 DHCC)

Glucocorticoids

Mineralocorticoids

Retinoic acid

Thyroid hormones (T3, T4)

2. Hormones that bind to cell surface receptors

A. Hormones that use cAMP as a 2nd messenger
1. Angiotensin II
2. Antidiuretic hormone
3. 2 adrenergic catecholamines
4. Parathyroid hormone
5. Glucagon
6. calcitonin
B. Hormones that use cGMP as 2nd messenger

Atrial natriuretic factor (ANF)

Nitric oxide (NO)

C. Hormone that use Ca

angiotensin II

2+

or phosphatidylinositol derivatives as 2nd messengers

Antiduretic hormone
1 adrenergic catecholamines
Acetylcholine

D. Hormones that use kinase or phosphatase cascade

insulin

Insulin like growth factors

Epidermal growth factor

Erythropoietin

Fibroblast growth factor

Nerve growth factor

Growth hormone

Cell signaling
Signaling molecules
Signaling molecules can generate specific response in its target cell to adapt the
changes in its environment. Signaling molecules are
1.
2.
3.
4.
5.
6.
7.

Hormones (major factor)

Growth factors
Cytokines
Cellular antigens & extracellular matrix
Special senses (sight, hearing, taste, smell, touch via neurotransmitters)
Gases ( NO, CO & free radicals)
Other physicochemical factors(pH, tension, temperature, osmolarity etc)

Signal transduction
Signal transduction is the process by which the message carried by signaling
molecule is accepted by (specific cell associated molecule called) receptor, then
transmitted via intracellular modulator and generate the appropriate responses of the
cells
Mechanisms of Action of Hormones/ General mechanism of cell signaling
Depend on type of receptors which in turns on solubility, hormones can be
divided into lipid soluble hormone & water soluble hormone
1. Mechanism of lipophilic signaling molecules
2. Mechanism of hydrophilic signaling molecules
A. that use ion channel linked receptors
B. that used G protein linked receptors
C. that used enzyme linked receptor

1. Mechanism of lipophilic signaling molecules

Signaling molecules are steroid hormones, thyroid H & retinoic acids

After secretion, hormone associates with transport proteins ( because of water

insoluble) & long plasma half-life

In plasma 2 forms--- bound & free form of Hormone

Because of lipid soluble in nature, free hormone transverses cell membrane and
binds to intracellular receptors (in cytoplasm or nucleus) of target cells.

forms a hormone-receptor complex. It is assumed to be the intracellular

messenger.

This complex(HRC) undergoes a temperature & salt dependent activation results

in size, conformation and surface charge changes

HRC moves into the nucleus and binds to hormone response element (HRE)
of a particular gene & activate or inactivate specific gene.

By selectively affecting gene expression production of mRNAspecific

proteininfluence metabolic process

HRE behave as enhancer or silencer

Regulate the gene expression, both in transcription as well as in translation

2. Mechanism of action of hydrophilic signaling molecules

They are water soluble in nature, so, no transport proteins is required & have
short plasma half-life

Hormones cannot pass through the cell membrane. So they bind to cell surface
receptor(membrane receptor). Their mechanism is mediated by intracellular
signals (second messengers). Hormones act as the first messenger that carry
information from endocrine gland to target cell and 2 nd messenger carry
information from cell membrane to metabolic processes.

This signals include cAMP, cGMP, Ca and phosphoinositides

(A)Mechanism of signaling molecules that use ion channeled linked receptors

Neurotransmitters bind to transmitter gated ion channels and convert chemical
signals into electrical potential at chemical synapse. Excitatory
neurotransmitters( acetylcholine, glutamate) open cation channel--- sodium influx
increases----- depolarization--- generate action potential.
Inhibitory neurotransmitters(GABA, glycine) open chloride channel and cause
hyperpolarization.
Strychnine( a toxin) binds to glycine receptors and block the action of glycine. This may
lead to muscle spasm, convulsion and death.

(B)Mechanism of signaling molecules that use G-protein linked receptors

Many hormones act via second messenger bind to G protein (GTP-binding

regulatory )
linked receptor. This mechanism needs 2nd messengers
for signal transduction of the cell.

Ligand binds to extracellular domain of receptor. Active receptor stimulates the G

protein.

Activated G protein activates membrane bound enzyme systems which generate

the 2nd messengers.

G protein is heterotrimeric (, and subunits). It couples the hormone receptor

to their target enzymes or ion channel in the plasma membrane.

Types of G protein (Depends on alpha subunit;

- Gs (s)

- stimulates adenylyl cyclase

- Gi (i) - inhibits adenylyl cyclase

- Gq (q) - stimulates phospholipase C

- G12 (12 )- Cl- channel.

Gs system - s-GTP stimulates adenyl-cyclase and cause increased in production of

cAMP which then activate protein kinase A. PKA phosphorylates target protein and
initiate a response in the cells. E.g ADH, calcitonin
Gi system - i-GTP inhibits adenyl cyclase and makes decreased in production of
cAMP. E.g 2 adrenergic , somatostatin

G q-GTP activates phospholipase C. Phospholipase C (PLC) cleaves PIP 2 to IP3 and

DAG. IP3 stimulates opening of Ca2+ channel in ER and generates Ca2+ signaling. DAG
stimulates PKC for cellular responses. E.g TSH, GnRH.
(C) Mechanism of Hormone Action through Enzyme linked Cell Surface
Receptor

Intracellular domain of receptor have intrinsic protein kinase action or is

associated with membrane bound protein kinase.

Signal is transmitted throughout the cell via protein kinases.

Cellular responses are related to growth and differentiation.

i)Enzyme Linked Receptor by guanylate cyclase

ANP or NO signaling

The receptor has gaunylate cyclase activity.

Stimulation of receptor generate cGMP.

cGMP activates PKG then generate cellular responses (e.g. vasodilation, smooth
muscle relaxation

ii)Actions through Tyrosine Kinase Receptor

Insulin, EGF & IGF-1 receptors have intrinsic tyrosine kinase activity. Binding of
hormone to receptor causes dimerization and cross phosphorylation on tyrosine
residue.

Then phosphorylated receptor phosphorylates the insulin receptor substrates

(IRS)

Phosphorylated IRS binds to the variety of proteins containing SH2 domain

iii)Mechanism of Action through Tyrosine-Kinase Associated Receptor

GH, erythropoietin and cytokines bind to tyrosine kinase associated receptor

Hormone receptor interaction promotes the binding and activation of

cytoplasmic protein tyrosine kinases . Then phosphorylation mechanism is
propagated

iv)Mechanism of Action through Tyrosine phosphatases

Activator protein-1
v)Mechanism of Action through serine threonine kinases
Transforming growth factor-
- 2ND MESSENGERS

2nd messengers are small intracellular molecules which are generated as

consequences of ligand receptor interaction and initiate a response in the cell.
( the hormone itself is the first messenger).

Second messenger concept-proposed by Earl W Sutherland in 1961. Epinephrine

bind to plasma membrane of pigeon RBC and increase intracellular cAMP

2nd Messengers are ----1)cAMP 2)cGMP 3)IP3 (inositol 1,4,5 triphosphat) 4) DAG
(1,2 diacyl glycerol)(5) Ca++
1. cAMP(cyclic adenosine monophosphate)
Formation --- when some hydrophilic hormone bind to G-protein linked receptor,
membrane bound G protein is activated which then activate membrane bound
adenylate cyclase that catalyzed the conversion of ATP to cAMP. Increased cAMP
activates cAMP dependent protein kinase(PKA) which further phosphorylate target
proteins and initiate cellular responses. In some animal cells an increase in cAMP
activates the transcription of specific gene through cAMP response element binding
(CREB) protein. Hormones such as ADH, glucagon, epinephrine(-adrenergic),etc exert
their action via cAMP. cAMP is degraded to 5 AMP by phosphodiesterase enzyme.

2.cGMP(cyclic guanosine monophosphate)

Formation ---when hormone bind to enzyme linked receptor, membrane bound
guanylate cyclase is activated which then convert GTP to cGMP. Increased cGMP
activate cGMP dependent protein kinase(PKG). PKG phosphorylates a number of smooth
muscle protein that result in smooth muscle relaxation and vasodilatation. Hormones in
this group include ANF and NO(nitric oxide).

3.Inositol triphosphate, DAG and Calcium.

TRH, TSH, GnRH, angiotensin,etc. bind membrane receptor and activate Gq

protein and then activate membrane enzyme phospholipase C .This enzyme
cleaves PIP2 to IP3 and DAG

IP3 stimulate the endoplasmic reticulum to release calcium

Calcium and calmodulin (Ca++ binding protein) complex activate Ca-M kinase &
DAG activate protein kinase C

CaM-kinase and PKC also phosphorylate target proteins and regulate the cellular
functions

CaM kinase activation can function as a molecular memory devices because it

remain active even after Ca++ is withdrawn.
G PROTEIN

It is GTP binding regulatory protein in cell membrane. G protein is heterotrimeric

protein composed of , & subunits.

G-protein is inactive when GDP is bound to subunit and active when GTP is
bound to subunit.

When hormone binds to a G-protein linked receptor, the receptor changes its
conformation and switches to active form ( to eject their GDP and replaces it
with GTP)

subunit which binds GTP dissociate from and subunits

The membrane bound enzyme is stimulated by -GTP . Stimulated enzymes

generate 2nd messengers (cAMP, IP3 ,DAG & Ca2+) and initiate response in the
cell.

The intrinsic GTPase activity of subunit converts the GTP to GDP which
inactivates the protein.

Alpha-GDP subunit is reassociated with & subunits

Types of G protein (Depends on alpha subunit)

- Gs (s)

- stimulates adenylyl cyclase

- Gi (i) - inhibits adenylyl cyclase

- Gq (q) - stimulates phospholipase C

- G12 (12 )- Cl- channel.

Gs & Gi System

Gs system - s-GTP stimulates adenyl-cyclase and cause increased in production

of cAMP

Gi system - i-GTP inhibits adenyl cyclase and makes decreased in production of

cAMP.

Gq system

Gq-GTP activates phospholipase C which cleaves PIP 2 to IP3 and DAG.

IP3 stimulates opening of Ca2+ channel in ER and generates Ca2+ signaling.

DAG stimulates PKC for cellular responses.

The responses are rapidly turned off by removal of external signal and break
down of GTP to GDP by GTPase
Biomedical Importance

Cholera toxin causes ADP-ribosylation to subunits of Gs and inhibit the GTPase

activity of s allowing adenylate cyclase in active state and enhances cAMP
production. This result in opening of electrolyte(Cl) channels in intestinal
mucosa and loss of water and NaCl from GIT.

Pertussis toxin catalyzed ADP-ribosylation to subunits of G i. Retains in

inactive state and unable to inhibit cAMP production.

G protein and Cancer

ras proteins (member of GTPase family ) that cycle between GTP and GDP forms

GTP forms stimulate cell growth and differentiationlead to cancer

BIOCHEMISTRY OF INSULIN

Insulin is a heterodimeric protein

Composed of 2 chains, A chain
(21 amino acids) and B chain (30
amino acids)
Two chains are linked by 2
interchain disulfide bridges ( A7 to
B7 and A20 to B19)
Third intrachain diulfide bridge ( A6
to A11)

Insulin gene is located at short arm of chromosome 11

Synthesized as preprohormone
Pre or leader sequences (23 amino acid) is removed in ER
Proinsulin is transported to the Golgi apparatus
Site specific peptide cleavages and form mature insulin and C- peptide
Zn2+ forms complex with insulin and proinsulin
Proteolysis and packaging into secretory granules
Upon appropriate stimulation, the mature granules fuse with plasma
membrane & discharge into blood by exocytosis

Regulation of insulin seceretion

Increase insulin secretion
After ingestion of glucose or CHO rich meal leads to rise blood
glucose( glucose is most important stimulant) . After ingestion of
protein( amino acids level in plasma). Hormone like Secretin , release after
the ingestion of food
Decrease insulin secretion
Scarcity of dietary fuel and trauma because of release of epinephrine
Transport and metabolism of insulin

Insulin has no plasma carrier protein. Metabolism occurs in liver (50%), kidney and
placenta.2 enzymes systems degrade insulin,1. insulin specific protea 2. glutathione
insulin transhydrogenase
Mechanism of insulin action

1.

Ther
e is
conf
orma
tiona

Insulin actions begin when the hormone binds to a specific glycoprotein

receptor on the surface of the target cell. The insulin receptor is a
heterodimer (22), glycoprotein in nature.

chan

2 2 linked by disulfide bonds

subunit is entirely extracellular and it binds insulin via a cystiene-rich
domain

ge
of

the

rece
ptor

subunit is transmembrane protein that performs signal transducer .

subunit has tyrosine kinase activity and an autophosphorylation site.

2.
When

insulin binds to the receptor

rece
ptors
cross
-link
and
form
micr
oagg
rega
tes
3.

Rece
ptor

When hormone binds receptor, tyrosine subunit of receptor is autophosphorylated. The

phosphorylated receptor next phosphorylates insulin receptor substarte(IRS).

is

Phosphorylated IRS

binds to the SH2 domains of a variety of proteins

inter

These proteins are docking proteins, kinases and phosphatases. The effect of
insulin on membrane transport, enzyme activity, gene expression and growth are
well known.

naliz

The action of insulin is terminated by dephosphorylation of receptor

ed

Metabolic effects of insulin

and

1.Effect on carbohydrate metabolism

dow

n
regul

Liver - decrease production of glucose

ated

Muscle & adipose tissue ------ increase glucose uptake

2. Effect on lipid metabolism

4.
One
Adipose tissue inhibit

lipolysis

or

3. Effect on protein metabolism -----Increase protein synthesis

Glucagon

more

Small peptide (29 amino acid)

Binds specific G protein linked receptor & cAMP is intracellular mediator of
action

sign

Metabolic effects of glucagon

als

increase blood glucose

Activate lipolysis

are

BIOSYNTHESIS OF HORMONES

gene
Biosynthesis of amino acid
derivative hormones

rate

Catecholeamine; - dopa,
dopamine, norepinephrine and
epinephrine

Thyroid hormones

BIOSYNTHESIS OF THYROID HORMONE

Thyroid Hormone biosynthesis involves thyroglobulin and iodide metabolism.
Thyroid hormones are synthesized from follicular cells of thyroid gland
Steps in biosynthesis
1. Concentration of iodide
2. Oxidation of iodide
3. Iodination of tyrosyl residues
4. Couplig of iodotyrosyls

5. Secretion

1. Concnetration of iodide
Concentrate iodide against a strong electrochemical gradient
Energy-dependent process and linked to ATPase-dependent Na +/K+ pump
(thyroidal I- pump)
The activity of pump is controlled by TSH
The ratio of iodide in thyroid to iodide in serum (T:S) ratio in human on a
normal iodine diet is about 25. The transport mechanism is inhibited by 2
classes
Perchlorate , Perrhenate and pertechnetate compete with iodide
Thiocyanate is a competitive inhibitor of iodide transport
2. Oxidation of iodide
Thyroid is only tissue that can oxidize iodide
An obligatory step in iodide organification and thyroid hormone biosynthesis
Involved a heme-containing peroxidase and H2O2
Iodide oxidation is inhibited by thiourea drugs
3. Iodiantion of tyrosyl residues
Oxdized iodide reacts with the tyrosyl residues in thyroglobulin. This reaction
is catalyzed by thyroperoxidase

 3 position of aromatic ring is iodinated first and then 5 position to form MIT
(monoiodotyrosine) and DIT (diiodotyrosine) respectively, catalyzed by
thyroperoxidase
Thyroglobulin is precursor of T3 and T4

4. Coupling of iodotyrosyls
Coupling of 2 DIT molecules to form T4
Coupling of one MIT and one DIT to form T3, catalyzed by thyroperoxidase
Thiourea also inhibit coupling
About 70% of iodide in thyroglobulin exists as MIT and DIT and 30% exist in
T4 and T3
5. Secretion
iodinated thyroglobulin are stored in extracellular colloid
After TSH or cAMP stimulation, there is marked increase of microvilli on
apical membrane
Microtubule-depedent process entraps thyroglobulin and pinocytose into the
follicular cell
Phagosome fuse with lysosomes to form phagolysosomes
Proteases and peptidases hydrolyzes thyroglobulin and T3 and T4 are
discharged from basal portion of cell into blood. About 50 g of thyroid
hormone is secreted each day
Mechanism of action of thyroid hormone
TH binds to intra nuclear receptor and HR complex binds to thyroid hormone
response element binding region(TRE) of DNA and regulate gene expression.TH
enhances the synthesis of sodium-potassium ATPase pump.
Biosynthesis of hormones of adrenal medulla
Catecholamines synthesized in chromaffin cells of adrenal medulla
Catecholamine (dopamine, norepinephrine and epinephrine)

80% is epinephrine

Biosynthesis of catecholamines ---------4 sequential steps

1. Ring hydroxylation
2. Decarboxylation
3. Side chain hydroxylation
4. N-methylation
1. Ring hydroxylation
Tyrosine is the immediate precursor of catecholamines
L- tyrosine converted to L-dopa(L-dihydroxyphenylalanine) by tyrosine
hydroxylase using tetrahydropteridine as a cofactor. Tyrosine hydroxylase is
rate limiting enzyme &feedback inhibition by catecholamines
This reaction is competitively inhibited by methyltyrosine
2. Decarboxyation
Dopa decarboxylase convert L-dopa to Dopamine (dihydroxyphenyl
ethylamine ) and coenzyme is pyridoxal phosphate.
Methyldopa is competitive inhibitors of this reaction
3. Side chain hydroxylation
Dopamine -hydroxylase (DBH) catlayzes conversion of dopamine to
norepnephrine
DBH uses ascorbate ,copper and fumerate for this reaction.
4. methylation

 Phenylethanolamine N-methyltransferase (PNMT) catalyzes the Nmethylation of norepinephrine to form epinephrine

PNMT is induced by glucocorticoid hormones
Catecholamines enter the chromaffin granules and stored
Neural stimulation of adrenal medulla results fusions of the membrane of the
storage granules and catecholamines are secreted to blood .
BIOSYNTHESIS OF HORMONES OF ADRENAL CORTEX
Adrenal cortex synthesizes 3 classes of Steroid hormone
Glucocorticoids (adaptation to severe stress)
Mineralocorticoids ( water and electrolytes balance or Na+ and K+ balance)
Androgen
Free cholesterol is transported to mitochondria where cytochrome P450 side
chain cleavage (SCC) enzyme (P450scc) covert it to pregnenolone (removal of 6
carbon). ACTH control this step
Glucocorticoids(cortisol) are synthesized in zona fasciculate. 3 key enzymes of
glucocorticoids synthesis are 17-hydroxylase, 21-hydroxylase and 11-hydroxylase
sequentially.
Mineralocorticoid(aldosterone) is synthesized in zona glomerulosa. 3 key enzymes of
mineralocorticoids synthesis are 21-hydroxylase, 11-hydroxylase and 18-hydroxylase
sequentially.
zona reticularis

zona glomerulosa

zona fasciculata

BIOSYNTHESIS OF GONADAL HORMONES

 Gonads are bifunctional organs, produce germ cells and the sex hormones
Testes produce spermatozoa and testosterone
Testicular androgen are synthesis by the Leydig cells
Immediate precursor of gonadal steroid is cholesterol
Pregnenolone to testosterone require actions of 5 enzyme and 2 pathways
5 (or) dehydroepiandrosterone

4 (or) progesterone pathway

BIOSYNTHESIS OF OVARIAN HORMONES

Ovaries produce ova, and steroid hormones , estrogens and progestrone

HORMONES THAT REGULATE CALCIUM METABOLISM

Total calcium in the body: approximately one kilogram
99% is located in bone as hydroxyapatite crystal
Provide the inorganic and structural component of skeleton
Normal blood calcium level:
- 2.1 to 2.6 (mmol/L) or 9 11 gm/dl
Plasma calcium exists as three forms- 1-complex with organic acids-2- bound with
albumin
3- ionized form (active form)
Hormonal regulation
- Parathyroid hormone
- Calcitriol (1,25 DHCC)
- Calcitonin

Parathyroid Hormone (PTH)

Decreased in plasma Ca2+ stimulates PTH synthesis

 Protein in nature & synthesized as preprohormone 115 amino acid residues.

Active hormone has 84 amino acids.
Mechanism of action
Cascade activation of adenylate cyclase . Increase cAMP level causing PTH
response
Actions of PTH
It restored normal ECF calcium concentration by acting directly on bone and
kidney and indirectly on the intestinal mucosa
Effects on bones
PTH promotes osteoclastic activity and formation of more osteoclasts
----Increase bone resorption
PTH increases calcium entry to osteocytes and osteoblasts. The osteoblast then
pumps calcium into ECF. The pump is stimulated by 1,25 DHCC.
Effects on kidneys
increase reabsorption of Ca++ in the distal tubules and decrease reabsorption of
phosphate in proximal tubules (phosphaturic action)
PTH also promotes formation of 1,25 DHCC in kidney by stimulating 1hydroxylase.
Intestine
PTH increase Ca++ absorption from intestine by promoting synthesis of 1,25
DHCC.
CALCITRIOL (1,25 DHCC)
It is steroid hormone.
MOA---by binding to
intranuclear receptor and
regulates the expression
of calcium binding
protein(calbidin)
synthesis.

ACTIONS OF CALCITRIOL
Effects on intestine
Increases calcium absorption from intestine by increasing the synthesis of
calbindin D
Effects on kidney
Facilitates Ca++ reabsorption in the kidneys
Effects on bone
It mobilizes Ca++ and increase the number of osteocalsts
stimulates osteoblast to produce osteoclastic resorption stimulating activity
(ORSA) and neutral protease
ORSA stimulates osteoclast and protease digest unmineralized bone

Calcitonin
peptide hormone (32 amino acids),,, secreted from parafollicular C cells of
thyroid gland.
Mechanism of action
By binding G-protein linked cell surface receptor and increases cAMP level.
Action of Calcitonin
Lowers circulating calcium and phosphate levels. It inhibits action of osteoclast
and decreases bone resorption. It Increases excretion of calcium in the urine.