Mechanism of Hormone action, Role of Secondary Messengers

cAMP, cGMP , Ca and Calmodulin.

PRESENTED BY JYOTI DEVENDRA ADALA

MSc PART 1

Coordination is the process through which two or more organs interact and complement the function of one another. Coordination is brought by the two following system:-

a) Nervous systemb) Endocrine system

INTRODUCTION TO HORMONES AND SECONDARY MESSENGERS

Hormones in Greek means to excite. Hormones are defined as the organic substance produced in small amounts by the endocrine glands secreted into the

blood stream to control metabolic and biological activities in the target cells.

Functions of the hormone include control of many metabolic pathway of various constituents, regulate secondary sexual characteristics and so on.

Secondary messengers are the molecules that relay signals from the receptors on the cell surface to target molecules inside the cell.

They greatly amplify the strength of the signal, cause some kind of change in activity of the cell.

Earl Wilbur Sutherland Jr., discovered secondary messengers for which he won the 1971 Noble Prize in medicine.

Hormones can classified into two groups

i) Based on their chemical nature

ii) Based on mechanism of action

a) Group 1 hormones- Bind to intracellular receptor to form complex and carry out biochemical function.

b) Group 2 hormones- Bind to cell surface receptor and stimulate the release of certain molecule namely secondary messengers which in turn perform biochemical function.

GROUP 1 HORMONE ACTION

Quick recap..Being lipophilic, these hormone can easily pass across the plasma membrane. They act through intracellular receptors ( cytosol or nucleus). They form hormone receptor complex binds to the specific regions on the DNA called HRE and cause increased expression of specific genes. It is believed that the interaction of hormone receptor complex with HRE promotes initiation , elongation and termination. The ultimate outcome is the production of specific proteins ( translation) in response to hormonal action.

GROUP 2 HORMONE ACTIONHormones that bind to surface receptors of the cells, communicate through intermediary molecules called second messenger which are generated as consequences of the hormone action.Example:- The heterotrimeric G protein. G protein was discovered by Alfred Gilman and Martin Rodbell in 1990.

MECHANISM OF SECOND MESSENGER1) Cyclic AMP ( adenosine 3’ 5’ monophosphate)cAMP synthesized from nucleotide ATP by the enzyme adenylate cyclase .

2) Cyclic GMP

cGMP (guanosine 3’ 5’ monophosphate) synthesized from nucleotide GTP by the enzyme guanylyl cyclase. Cyclic GMP carries different messages to different tissues:1) In the kidney and intestine,2) In the cardiac muscle it signal relaxation,3) Nitric oxide stimulates the synthesis of cyclic

GMP.

3. CALCIUM AND/ OR PHOSPHOINOSITIDES AS SECONDARY MESSENGER

In many cells that respond to extracellular signals, calcium serves as a second messenger.

Certain hormone receptor interaction result in activation of the enzyme phospholipase C through a specific G protein.

Intracellular enzyme phospholipase C hydrolyzes phosphotidylinositol-4,5 bisphosphate (PIP2) which is found in inner layer of the plasma membrane. Hydrolysis of PIP2 yield two productsa) Diacylglycerol ( DAG)b) Inositol -1,4, 5 triphosphate ( IP3)

Schematic representation of hormone action by way of phosphatidylinositol or calcium as second messenger

4. CALMODULIN AS SECONDARY MESSENGER

Calcium calmodulin second messenger system operates in response to the entry of calcium into the cells.

Calmodulin is an acidic protein with highly conserved single polypeptide chain has four high affinity for calcium binding sites.

Binding of calcium causes profound conformational changes in calmodulin’s affinity for its effector molecules.

Calmodulin, when activated, causes contraction of smooth muscles.

CONCLUSIONHormones are the chemical messengers that bind to intracellular receptor or cell surface receptor to form complex and carry out biochemical function.

Hormones that bind to surface receptors of the cells, communicate through intermediary molecules called second messenger which are generated as consequences of the hormone action.

Signal transduction pathways allow cells to respond to environmental signals. In these pathways, a signal is amplified.

This signal amplification is brought about by second messengers like cAMP, cGMP, calcium ions, calmodulin, DAG and IP3.

Second messengers essentially serves as chemical relays from the plasma membrane to cytoplasm, thus carrying out the intracellular signal transduction.

REFERENCES

- ESSENTIALS OF MEDICAL BIOCHEMISTRY- SECOND EDITION BY R C GUPTA

- ESSENTIALS OF BIOCHEMISTRY BY PANKAJA NAIK- PHYSIOLOGY BY JOSHI MENDHURWAR- PRINCIPLES OF BIOCHEMISTRY BY LEHNINGER- PRINCIPLES OF ANATOMY AND PHYSIOLOGY BY

TORTORA- CELL AND MOLECULAR BIOLOGY BY KARP GERALD