MECHANISM OF ACTION OF HORMONES

2.  The hormone is “substances released from
ductless or endocrine glands directly to the
blood”.
 A more modern definition of a hormone is
that it is synthesized by one type of cells &
transported through blood to act on another
type of cells.

3.  Signal Transduction through G protein:
 Action is through G protein coupled
receptors (GPCR).
 Action of several hormones is effected
through this mechanism.
 The GPCRs are transmembrane proteins with
7 helical segments spanning the membrane.

4.  When any ligand binds, GPCRs activate heterotrimeric
GTP binding regulatory proteins (G-proteins).
 The G-protein will interact with effector proteins
which may be enzymes or ion channel proteins, which
result in the desired effect.
 Different types of G proteins are present in the cells
that are coupled with different receptors & activating
different effector proteins.

5.  The extracellular messenger, the hormone (H)
combines with the specific receptor (R) on the
plasma membrane.
 The H-R complex activates the regulatory
component of the protein designated as G-protein or
nucleotide regulatory protein.
 G proteins – they can bind GTP & GDP.
 The G-protein is a membrane protein consisting of α,
β and γ subunits.

7.  When the hormone receptor complex is formed, the
activated receptor stimulates the G protein, which
carries the excitation signal to adenylate cyclase.
 The hormone is not passed through the membrane; but
only the signal is passed; hence this mechanism is
called signal transduction.
 The adenyl cyclase is embedded in the plasma
membrane.

8.  When activated, GTP binds & β-γ subunits dissociate
from the α subunit.
 Adenylate cyclase is activated by Gα – GTP.
 The binding of hormone to the receptor triggers a
configurational change in the G protein which induces
the release of bound GDP & allows GTP to bind.
 The hormone has an amplified response, since several
molecules of Gα – GTP are formed.

10.  The active Gα – GTP is immediately inactivated by
GTPase.
 The Gα – GDP form is inactive.
 The activation is switched off when the GTP is
hydrolysed to GDP by the GTPase activity of the α
subunit.
 The α subunit, which is bound to GDP, can re-
associate with β and γ subunits.
 The GTP-GDP exchange rate decides the activity of
adenyl cyclase.

12.  Adenyl cyclase or adenylate cyclase converts
ATP to cAMP (3',5'-cyclic AMP) &
phosphodiesterase hydrolyses cAMP to 5' AMP.
 Cyclic AMP is a second messenger produced in
the cell in response to activation of adenylate
cyclase by active G protein.
 During hormonal stimulation, cyclic AMP level
in the cell increases several times.

14.  Acts as second messenger in the cell.
 Regulates glycogen metabolism – increased
cAMP produces breakdown of glycogen
(glycogenolysis).
 Regulates TGL metabolism – increased cAMP
produces lipolysis (breakdown of TGL).
 cAMP stimulates protein kinases.
 cAMP modulates transcription & translation.

15.  cAMP involved in steroid biosynthesis.
 cAMP regulates permeability of cell
membranes to water, Na+, K+ & calcium.
 Involved in regulation insulin secretion,
catecholamine & melatonin synthesis.
 Histamine increases cAMP, which increases
gastric secretion.

16.  cGMP involved in phosphorylation of
proteins. E.g. acetyl choline in smooth muscle.
 Role in vasodilation:
 Nitroglycerine, cerine, sodium nitrite etc.
causes smooth muscle relaxation &
vasodilation by increasing cGMP.
 Role in action of neurotransmitters:
 GABA has been claimed to change cGMP
levels in cerebral tissues.

17.  Role in prostaglandin synthesis:
 PG-F2 require cGMP for its action.
 Role in insulin actions:
 Insulin action in some tissues is mediated
through cGMP, which activates protein
kinases.
 Role in vasodilation produced by nitric oxide:
 NO produces vasodilation & lowering BP by
increasing cGMP.

18.  Calcium is intracellular regulator of cell
function.
 Intracellular calcium level is low than
extracellular calcium.
 3 types of calcium transport systems:
 Voltage gated calcium channel.
 Sodium/calcium antiport transporter.
 Calcium transporting ATPase.

19.  This type of signal transduction is
phospholipase C that hydrolyses
phosphatidyl inositol to 1,4,5-Inositol
triphosphate (IP3) & Diacyl Glycerol (DAG) that
act as second messengers.
 PIP3 (Phosphatidyl Inositol 3,4,5- phosphate) is
another second messenger produced by the
action of a phosphoinositide kinase.

20.  The phospholipase C may be activated either
by G proteins or calcium ions.
 DAG can also be generated by the action of
phospholipase D that produces phosphatidic
acid which is hydrolyzed to DAG.

21.  The steroid & thyroid hormones are included
in this group.
 They diffuse through plasma membrane &
bind to the receptors in the cytoplasm.
 The hormone receptor (HR) complex is
formed in the cytoplasm.

22.  The complex is then translocated to the
nucleus.
 Steroid hormone receptor proteins have a
molecular weight of about 80-100 kD.
 Each monomer binds to a single steroid
molecule at a hydrophobic site, but on
binding to genes they dimerise.

23.  The HR complex binds to HRE (hormone
responsive element).
 HRE increase transcriptional activity.
 Newly formed mRNA is translated to specific
protein, which brings metabolic effects.
 Steroid hormones influence gene expression
& rate of transcription is also increased.

24.  Textbook of Biochemistry – DM Vasudevan
 Textbook of Biochemistry – U Satyanarayana
 Textbook of Biochemistry – MN Chatterjea