Melatonin Membrane Receptors in Peripheral Tissues: Distribution and Functions

Many of melatonin’s actions are mediated through interaction with the G-protein coupled membrane bound melatonin receptors type 1 and type 2 (MT1 and MT2, respectively) or, indirectly with nuclear orphan receptors from the RORα/RZR family. Melatonin also binds to the quinone reductase II enzyme, previously defined the MT3 receptor. Melatonin receptors are widely distributed in the body; herein we summarize their expression and actions in non-neural tissues. Several controversies still exist regarding, for example, whether melatonin binds the RORα/RZR family. Studies of the peripheral distribution of melatonin receptors are important since they are attractive targets for immunomodulation, regulation of endocrine, reproductive and cardiovascular functions, modulation of skin pigmentation, hair growth, cancerogenesis, and aging. Melatonin receptor agonists and antagonists have an exciting future since they could define multiple mechanisms by which melatonin modulates the complexity of such a wide variety of physiological and pathological processes

Pineal melatonin and the innate immune response: the TNF-alpha increase after cesarean section suppresses nocturnal melatonin production

The nocturnal surge of melatonin is the endocrine expression of the circadian system and is essential for organizing the timing of various endogenous processes. Previous works suggest that, in the beginning of a defense response, the increase in circulating tumor necrosis factor-alpha (TNF-alpha) leads to a transient block of nocturnal melatonin production and promotes a disruption of internal time organization. in the present paper, the concentration of melatonin and cytokines [TNF-alpha, interferon-gamma (IFN-gamma), interleukin (IL)-2, IL-4, IL-5, IL-10, IL-12] in the colostrum (postdelivery day 3) and in the milk (postdelivery days 10, 15, 20 and 30) obtained at midday and midnight from mothers who gave birth by vaginal or cesarean section were compared. the nocturnal melatonin surge observed 3 days after vaginal delivery was absent after cesarean section. IL-12 presented no daily variation in either case, while daily variations in IFN-gamma, IL-10, IL-4 and IL-5 were observed after vaginal delivery and cesarean section. On the other hand, the increase in TNF-alpha after cesarean section resulted in suppression of the nocturnal melatonin surge. Daily variation of IL-2 was only observed after recovery of the nocturnal melatonin surge, 30 days after cesarean section. the present paper supports the hypothesis of a cross-talk between the pineal gland and the immune system, which could represent a putative immune-pineal axis.Univ São Paulo, Lab Chronopharmacol, Dept Fisiol, Inst Biociencias, BR-05508900 São Paulo, BrazilUniv São Paulo, Lab Mucosal Immunol, Dept Immunol, Inst Biomed Sci, BR-05508900 São Paulo, BrazilUniv São Paulo, Dept Pediat, Sch Med, BR-05508900 São Paulo, BrazilWeb of Scienc