THE SLIDE EXPLAINS ABOUT THE HORMONAL REGULATION, DIFFERENT CLASSES OF HORMONES , SYNTHESIS OF HORMONES AND NEUROENDOCRINE INTERACTION.

1. Principle of endocrinology

2. Functions of hormones and their regulation
What are hormones?.
Hormones are low molecular weight, chemically heterogenous non-nutrient
substances which produced in trace amount and act as intercellular signal molecules.
Specific target cells can respond to each hormone because only the target cells have
receptors for binding with the particular hormone.
Hormone signalling involves the biosynthesis of a particular hormone in a particular
tissue, storage and secretion of the hormone, transport of the hormone to the target
cell(s), recognition of the hormone by an associated cell membrane or intracellular
receptor protein, rely and amplify of the received hormonal signal via a signal
transduction process and a cellular response.

3. •The secretion of hormone is
subject to negative feedback
control. Disturbances in
feedback loops are clinically
important and their
significance in diagnosis is
pivotal.
•Most hormones are
controlled by negative
feedback, in which the
hormone feeds back to
decrease its own
production. This type of
feedback brings things
back to normal whenever
they start to become too
extreme.
•Positive feedback is
much less common
because it causes
HORMONAL REGULATION

4. Chemical classification of hormones
Hormones are chemically heterogenous and derive from diverse precursors such as amino
acids, cholesterol or phospholipids. They can be divide into two broad classes:
Lipid-soluble hormones
Eg-steroid hormones and thyroid hormones.
1. Steriod hormones are derived from cholesterol.
2. Thyroid hormones(T3 and T4) are synthesised by attaching iodine to the amino acid
tyrosin. The benzene ring of tyrosin make T3 and T4 lipid soluble.
Water soluble hormones
Eg- amine hormones, peptide or protein hormones.
1. Amine hormones are synthesized by decarboxylation or modification of certain amino
acids. The catecholamines- epinephrine, norepinephrine and dopamine-are synthesied
by modifying the amino acid tyrosine. Histamine is synthesied from the amino acid
histidine by mast cells and platlets. Serotonin and melatonin are derived from
tryptophan.
2. Peptide hormones and protein hormones- eg of peptide hormones are ADH and
oxytocin, protein hormones include HGH and insulin. TSH is a glycoprotein hormones.

6. Peptide Hormone synthesis
Events during hormone
synthesis
1) Transcription of gene
2) Post-transcriptional
modification by exision of
the
Introns.
3) Translation of the mRNA
and post-translational
modifications of the original
amino acid sequence. As a
result, more
than one pro-hormone may be
derived from a single gene.
Furthermore, post-translational
processing of a pro-hormone
may result in the formation of
different biologically active
peptide
fragments. These processes are
typically tissue-specific

7. Events during hormone synthesies
1) The removal of a six-carbon unit from
the side chain of cholesterol to
form pregnenolone.
 Progesterone is synthesized from
pregnenolone in two steps. The 3-
hydroxyl group of pregnenolone is
oxidized to a 3-keto group, and the
Δ5 double bond is isomerized to a
Δ4 double bond.
 cortisol is formed by hydroxylations
at C-17, C-21
 aldosterone, the major mineralocorticoid,
the hydroxylation of progesterone at C-21
takes place. The resulting
deoxycorticosterone is hydroxylated at C-
11. The oxidation of the C-18 angular
methyl group to an aldehyde then yields
aldosterone.
Steroid Hormone synthesis

8. The Synthesis of Androgens and Estrogens from
Pregnenolone
 The synthesis of androgens starts with the hydroxylation
of progesterone at C-17. The side chain consisting of C-
20 and C-21 is then cleaved to
yield androstenedione, an androgen. Testosterone, is
formed by the reduction of the 17-keto group of
androstenedione. Testosterone is reduced by 5a-
reductase to yield dihydrotestosterone (DHT), a
powerful embryonic androgen that instigates the
development and differentiation of the male phenotype.
 Estrogens are synthesized from androgens by the loss of
the C-19 angular methyl group and the formation of an
aromatic A ring.

9. Transport of hormones in the circulation and their half-lives
• Lipid soluble hormones usually circulate in blood as complexes bound to specific
plasma globulins or albumin but the unbound or free hormone is biologically
active.
• Hormone binding delays metabolism and provides a circulating reservoir of
hormones.
• The rates of metabolism of hormones in the circulation vary but generally the half
life (t/2 ) of catecholamines is in the order of seconds, minutes for protein and
peptide hormones and hours for steroid and thyroid hormones.

10. Hormone receptors - cell surface
• Receptors are integral transmembrane proteins in the plasma membrane. When
a water soluble hormone bind to its receptor at the outer surface of the plasma
membrane, it acts the first messenger. The first messenger (the hormone) the
causes production of a second messenger (including cAMP, cGMP, diacylglycerol,
inositol triphosphate, phosphoinositides and calcium) inside the cell, where the
specific hormone-stimulated response take place.
• The majority of classical protein and peptide hormone receptors are the G-
protein linked receptors.
These may either have a relatively
short extracellular amino terminal
domain (e.g.
epinephrine, GnRH) or a much
longer extracellular domain (e.g.
TSH, LH, PTH)

12. Signal transduction pathways for cell surface receptors
MEK-MAPK pathway

13. Hormone receptors - intracellular
The characteristic single polypeptide
chain is structurally and functionally
divided into six domains:
 At the amino terminus are
the A/B domains that are variable both
in sequence and length.
 The C domain, also called the DNA
binding domain (DBD), is
a highly conserved sequence across all
steroid receptors and is characterized by
possessing two zinc fingers which
readily slot into the helix of the DNA
molecule.
 The D domain is thought to represent
a hinge region in the molecule
 E represents the ligand binding
domain
 F a variable region in the carboxyl
terminus. This end of the molecule is
also the region where the
heat shock proteins (hsps) are bound
and where dimerization occurs.

14. Receptor types
 Receptors that exist predominantly in
the cytoplasm are classified as Type 1
receptors and these include the
glucocorticoid, mineralocorticoid,
androgen and progesterone receptors.
 They are bound to heat shock proteins
(e.g. hsp 90, hsp70 and hsp 56).
 Upon steroid binding the hsp complex
is released and the receptor forms a
dimer with another identical receptor .
The homodimer translocates to the
nucleus where it binds to a specific
base sequence on the DNA.

15.  Type 2 receptors are typically located in the nucleus and may be bound to DNA. They
characteristically form heterodimers (e.g. thyroid hormone receptor and retinoid X receptor) or
may initiate transcription as monomers upon ligand binding.

16. Hormone receptor regulation
• Receptor regulation occurs through up or down-regulation of the number of receptors and by
desensitization of the receptors. This occurs by increasing or decreasing receptor synthesis, by
internalization of membrane receptors after ligand binding, or by uncoupling of the receptor from
its signal transduction pathway (desensitization).
• Some hormones may regulate their own receptors (homologous regulation) such as GnRH on the
pituitary gonadotrophs whilst other receptors are regulated by other hormones (heterologous
regulation) e.g. estrogen regulating oxytocin receptors.
• Interaction between hormones and their receptors depends on:
the number of receptors,
 the concentration of circulating hormone and
 the affinity of the hormone for the receptor.

17. Neuroendocrine interactions
• All endocrine glands are innervated by autonomic nerves and these may either directly control their
endocrine function and/or regulate blood flow (and hence function) within the gland. Hormones, in
turn, may affect central nervous system functions such as mood, anxiety and behavior.
• Neurosecretory cells may directly convert a neural signal into a hormonal signal. In other words
they act as transducers converting electrical energy into chemical energy. Thus, activation of
neurosecretory cells leads to secretion of a hormone into the circulation.
• These neurosecretory cells include: those that secrete hypothalamic releasing and inhibiting
hormones controlling TSH, ACTH, LH and FSH release from the anterior pituitary gland; the
hypothalamic neurons the axon terminals of which secrete oxytocin and vasopressin from the
posterior pituitary gland; the chromaffin cells of the adrenal medulla (embryologically modified
neurons) that secrete epinephrine and norepinephrine into the general circulation

18. Thank You
Presented by-Nidha parveen