Molecular Mechanism of Hormone Action
The foregoing discussion indicated that hormones belong to different groups of chemical substances; some are simple modified amino acids, some peptides, some complex polypeptides and proteins and some other steroids. These hormones bring about a variety of biological actions leading to diverse physiological regulations; often the same hormones have different effects in different organ systems and tissues. Thus, it may be possible that all hormones may not have the same mechanism of action and it is quite probable that they differ in the mechanisms by which the effects in the target tissues are brought about. However, it has been found that there are certain common features in the action of many hormones which enable us to generalise the mechanisms by which hormones act at the cellular level.
It is thought that, at least in the case of some of the hormones the mechanism is by selective activation of genes and consequent control over protein (enzyme) synthesis. However the actions of some of the hormones are not mediated through gene activation and may be through activation of specific enzymes located on the cell membrane or in the cytoplasm, outside the cell nucleus. In either of these two modes of actions of hormones the first and foremost step in hormone action is that the hormone attaches to a specific molecule, a protein, in the target cell. This molecule has been named as the hormone receptor which shows specificity for specific hormones. The complex molecule of the hormone with the receptor is known as hormone-receptor-complex. The mechanism by which the hormone-receptor-complex brings about the biological action of the hormone depends on the type of hormone.
Interaction with Plasma Membrane Receptors
One mechanism of hormone action involves an interaction at the cell surface between the hormone and a receptor at a receptor site on the plasma membrane. A hormone released from the endocrine gland circulates in the blood, reaches a target cell, and brings a specific message to that cell. The hormone is called the first messenger. To give the cell its message, the hormone must attach to a specific receptor site (integral protein) on the plasma membrane. This attachment can alter cell function by two different pathways.
In one pathway there is an increase in the synthesis of cyclic adenosine -3', 5' -monophosphate (cyclic AMP). Cyclic AMP is synthesised from ATP. This synthesis requires an enzyme present in the plasma membrane called adenyl cyclase. When the first messenger (hormone) attaches to its receptors, there is an activation of adenyl cyclase, resulting in the conversion of ATP into cyclic AMP in the cell. Cyclic AMP then diffuses throughout the cell, binds to an intracellular receptor, and acts as second messenger, altering cell function according to the message indicated by the hormone. Cyclic AMP can activate the appropriate cellular enzymes to get a specific biochemical response. Calcium ions may sometimes be involved as second messengers along with cyclic AMP. Cyclic AMP can also stimulate protein synthesis, induce secretion and alter membrane permeability. High levels of cyclic AMP persist only briefly because it is rapidly degraded by cyclic AMP phosphodiesterase. Since prostaglandins also can stimulate the formation cyclic AMP, they also have a role in the regulation of the action of hormones.
Mechanism of Hormone Action: Interaction with Plasma Membrane Receptors in which there is an Increase in the Synthesis of Cyclic AMPMost water soluble hormones exert their effects by the path way of increasing the synthesis of cyclic AMP. These include antidiuretic hormone (ADH), oxytocin, follicle stimulating hormone (FSH), luteinising hormone (LH), thyroid stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), calcitonin (CT), parathyroid hormone (PTH), glucagon, epinephrine and norepinephrine (NE).
The binding of a few water soluble hormones insulin, growth hormone (GH) and prolactin (PRL) to their plasma membrane receptors does not lead to an increase in cyclic AMP. In an alternate pathway, the levels of cyclic AMP remain unchanged or decrease. Some evidence suggests that insulin, growth hormone and prolactin may actually enter target cells and attach to various intracellular structures.
Unlike catecholamine and peptide hormones, steroid 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.