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