Abstract
The pineal hormone melatonin has attracted great scientific interest since its discovery in 1958. Despite the enormous number of basic and clinical studies the exact role of melatonin in respect to human physiology remains elusive. In humans, two high-affinity receptors for melatonin, MT1 and MT2, belonging to the family of G protein-coupled receptors (GPCRs) have been cloned and identified. The two receptor types activate Gi proteins and MT2 couples additionally to Gq proteins to modulate intracellular events. The individual effects of MT1 and MT2 receptor activation in a variety of cells are complemented by their ability to form homo- and heterodimers, the functional relevance of which is yet to be confirmed. Recently, several melatonin receptor genetic polymorphisms were discovered and implicated in pathology—for instance in type 2 diabetes, autoimmune disease, and cancer. The circadian patterns of melatonin secretion, its pleiotropic effects depending on cell type and condition, and the already demonstrated cross-talks of melatonin receptors with other signal transduction pathways further contribute to the perplexity of research on the role of the pineal hormone in humans. In this review we try to summarize the current knowledge on the membrane melatonin receptor activated cell signaling in physiology and pathology and their relevance to certain disease conditions including cancer.
Highlights
Received: 30 November 2021Melatonin (N-acetyl-5-methoxytryptamine) is a hormone secreted by the pineal gland, which plays important role in a wide array of physiological processes in mammals [1]
The functional activity of melatonin has a broad spectrum of action, with some of its functions still being studied
A reduction in the MT2-mediated decrease in alkaline phosphatase enzyme activity is observed when the MT2 receptors are completely desensitized, suggesting that a decrease in receptor sensitivity is a necessary step in the above differentiation [57]. These findings suggest that human MT1 and MT2 receptors can be desensitized under the influence of circulating melatonin in a manner similar to that observed in animals
Summary
Melatonin (N-acetyl-5-methoxytryptamine) is a hormone secreted by the pineal gland, which plays important role in a wide array of physiological processes in mammals [1]. Well documented findings on the biological significance of the hormone in mammals include control of retinal function, control of reproductive cycles in seasonally breeding animals and influence on the phases of 24-h behavioral rhythms (e.g., sleep-wake cycle), and participation in the control of thermoregulation and sleep. These functions are thought to be mediated by specific melatonin receptors. Two different G-protein-coupled receptors which bind melatonin with high affinity have been identified and characterized [7,8] They are thought to regulate a wide array of physiological activities in response to the rhythmic secretion of melatonin from the pineal gland. A major drawback in studies focused on melatonin receptor signaling is the inability to identify a physiological stimulus associated with the activation of melatonin receptor-driven intracellular transduction
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