GPCR Signalling Pathway: Hormone Action as a Second Messenger System

Introduction:

G protein-coupled receptors (GPCRs) are a large family of membrane receptors that are involved in a wide range of physiological processes, including hormone action.

GPCRs act as a second messenger system, transmitting signals from extracellular molecules (such as hormones) to intracellular effectors (such as enzymes and ion channels) to elicit a response.

Step 1: Hormone binding to GPCR:

Hormones bind to their specific GPCRs on the cell surface, leading to a conformational change in the receptor.

Depending on the type of hormone and receptor, this binding can either activate or inhibit the receptor.

Step 2: Activation of G protein:

Activation of the GPCR leads to the exchange of GDP for GTP on the G protein.

This causes the G protein to dissociate into its active Gα and Gβγ subunits.

Step 3: Signal transduction:

The Gα subunit can then activate or inhibit intracellular effectors, depending on its specific type (Gαs, Gαi, Gαq, etc.).

Gαs activates adenylyl cyclase, which converts ATP to cAMP, a second messenger that activates protein kinase A (PKA). PKA then phosphorylates target proteins.

Gαi/o inhibit adenylyl cyclase, thereby decreasing cAMP levels.

Gαq activates phospholipase C, which hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) to generate inositol triphosphate (IP3) and diacylglycerol (DAG). IP3 triggers the release of intracellular calcium stores, while DAG activates protein kinase C (PKC).

Step 4: Termination of signal:

The Gα subunit hydrolyzes the bound GTP to GDP, causing it to reassociate with the Gβγ subunit and inactivate.

cAMP is rapidly degraded by phosphodiesterase, thereby reducing its levels.

Calcium ions are actively pumped out of the cell, or stored back into intracellular compartments, thereby reducing the levels of intracellular calcium.

Step 5: Cellular response:

The cellular response to the hormone can be a wide range of effects, depending on the specific target proteins and pathways activated.

For example, the hormone may lead to changes in gene expression, changes in enzyme activity, changes in ion channel activity, changes in cell proliferation, changes in cell migration, etc.

Conclusion:

GPCR signalling pathway is a key mechanism by which hormones exert their effects on cells.

By understanding the specific steps in the pathway, scientists can gain insight into how hormones regulate physiological processes and develop new strategies for treating diseases that involve hormone imbalances.