Nuclear melatonin receptors

Abstract

Melatonin is a hormone produced in the central nervous system (pineal gland) and peripheral tissues (appendix, pancreas, adrenal glands, thymus, prostate, ovaries, placenta). It is secreted by blood cells (platelets, lymphocytes and eosinophils) and endothelium. Melatonin is found in mast cells, endometrium, cerebellum, neuroendocrine cells of the airways, paraganglia, inner ear, liver, gallbladder, cortical layer of the kidneys. The key role of melatonin is determined by the fact that endogenous rhythms of the body are subordinated to the rhythms of its production. The number of melatonin publications is constantly increasing, indicating the versatility of its effects resulting from its active participation in many physiological and pathological processes. There is convincing evidence that melatonin participates in almost all vital processes that control many body functions, including sleep and activities of the immune, endocrine, and cardiovascular systems. This is manifested by the universal therapeutic properties of melatonin, which, in turn, are determined by its peculiar biological role. Since melatonin easily traverses biological membranes, it can exert its effect in almost all cells. Some of its effects are receptor-mediated, others are receptor-independent. The main effects of melatonin are associated with its effect on the membrane receptors, MT1 and MT2, that belong to the family of receptors associated with G-proteins. These receptors are responsible for chronobiological effects and regulation of circadian rhythms. MT1 and MT2 are present in peripheral organs and cells, and they contribute, for example, to some extent to immunological reactions and vasomotor control. MT1 is more responsible for vasoconstriction, while MT2 causes vasodilation. The nuclear melatonin receptors, ROR-α/RZR-β, have been discovered relatively recently. Apparently, many immune-stimulating and antitumor effects of melatonin are mediated through them. The antioxidant function of melatonin is partially based on receptor interaction, but some antioxidant properties do not require participation of the receptor apparatus. This review examines and discusses the information available in the Russian and international literature on the potential role of orphan nuclear retinoid receptors of the ROR/RZR subfamily in regulating the activity of the pineal hormone melatonin. The mechanisms of receptor-DNA interaction and known coactivators, tissue-specific features of the expression of various isoforms of the receptor, and its regulation are described. The array of probable targets for regulation by receptors is analyzed, the most common of which are the lymphoid and central nervous systems. The review identifies some prospects for further study of melatonin receptors.