Melatonin receptors in reproductive tissues: Evidence for the multiple sites of melatonin action

Abstract

Pineal melatonin in the circulation plays an important role in the synchronization of seasonal animal reproduction. However, the target sites of pineal melatonin action on the reproductive system have to be elucidated. Earlier reports have documented the hypothalamic-pituitary axis to be the essential sites of melatonin regulation. Melatonin receptors have been demonstrated in the suprachiatasmatic nuclei (SCN) and pars tuberalis (PT). How the SCN or PT mediate melatonin action on the GnRH, LH and/or FSH remains speculative. In addition to SCN and PT, other sites in the reproductive system may be involved. Using the specific melatonin agonist, 2[125I]iodo-melatonin, putative melatonin receptors have been identified in different reproductive tissues including the testis, epididymis, vas deferens, prostate, ovary, and mammary gland by autoradiography (ARG) and radioreceptor binding assays. These sites are saturable, stable, reversible, specific and of high affinity. 2[125I]iodomelatonin appeared to bind to a single class of site in membrane preparations of reproductive tissues as demonstrated by the linearity of the Scatchard plot and the unity of Hill coefficient. Affinities of 2[125I]iodomelatonin binding sites in the reproductive tissue membranes are in the picomolar range suggesting that these sites are physiologically relevant, as the circulating levels of melatonin are in the picomolar range. The densities and/or affinities of 2[125I]iodomelatonin binding sites change with pharmacological and/or physiological variations. Recent studies have revealed melatonin-induced biological responses and the presence of melatonin receptor subtypes in the testis, epididymis, prostate, mammary gland and granulosa cells. These findings support the hypothesis of multiple sites of melatonin action on the reproductive system. Melatonin action on multiple reproductive sites may generate a synergistic or summative effect on the reproductive system constituting a robust combination of photoperiodic control on animal reproduction. This maximizes the use of a reliable environmental information (the photoperiod) and ensures the survival of species (reproduction).