Mechanism of hormone action

Mechanism of Hormone Action

Catecholamines, peptide and protein hormones are not lipid-soluble, and so, cannot enter their target cells through the bilipid layer of plasma membrane.

Instead, these water soluble hormones interact with a surface receptor, usually a glycoprotein, and thus, initiate a chain of events within it.

The hormone insulin provides a well-studied example.

Extracellular Receptor:

The membrane bound receptors of insulin is a heterotetrameric protein consisting of four subunits, two a-subunits protrude out from surface of the cell and bind insulin, and two b-sub-unit that span the membrane and protrude into the cytoplasm.

Binding to the receptor:

Binding of insulin to the outer subunits of the receptor causes a conformational change in the membrane spanning b-subunits, which is also an enzyme, a tyrosine kinase.

The activated b-subunits add phosphate groups of specific tyrosine residues located in cytoplasmic domain of the receptor as well as a variety of insulin receptor substrates.

Second messengers-the mediator:

As a result of b-subunit activity, a transducer G-protein activates enzyme phosphodiesterase.

This enzyme breaks phosphatidylinositol 4,5-biphosphate (PIP₂) into a pair of mediators: inositoltriphosphate (IP₃) and diacylglycerol (DG).

In turn, IP₃, which is water-soluble, and so diffuses into cytoplasm and triggers the release of another messenger Ca²⁺ ions for intracellular calcium­mediated processes.

While DG remains within the membrane where it activates an enzyme called protein kinase C, which in turn, activates many other enzymes, such as pyruvate dehydrogenase, and so brings about the physiological effects.

Antagonistic effect:

Many cells use more than one second messenger.

In heart cells, cAMP serves as a second messenger, speeding up muscle cell contraction in response to adrenaline, while cyclic guanosine monophosphate (cGMP) serves as another second messenger, slowing muscle contraction in response to acetylcholine.

It is in this way that the sympathetic and parasympathetic nervous systems achieve antagonistic effect on heartbeat.

Another example of antagonistic effect is insulin, which lowers blood sugar level, and glucagon, which raises it.

Synergistic effect:

Another type of hormonal interaction is known as synergistic effect.

Here, two or more hormones complement each other's actions and both are needed for full expression of the hormone effects.

For example, the production, secretion and ejection of milk by mammary gland require the synergistic effect of estrogens, progesterone, prolactin and oxytocin.

Intracellular Receptors:

Unlikely catecholamine and peptide hormones, steroid and thyroid hormones are lipid-soluble hormones and readily pass through the plasma membrane of a target cell into the cytoplasm.

There they bind to specific intracellular receptor proteins, forming a complex that enters the nucleus and bind to specific regulatory sites on chromosomes.

The binding alters the pattern of gene expression, initiating the transcription of some genes (DNA), while repressing the transcription of others.

This results in the production of specific mRNA translation products, proteins and usually enzymes.

The actions of lipid-soluble hormones are slower and last longer than the actions of water-soluble hormones.

These cause physiological responses that are characteristic of the steroid hormones.