Besides the hypothalamus and pituitary, melatonin action at the testicular level has been recently suggested. Therefore, we investigated in the Syrian hamster, a well-characterized seasonal breeder, (a) melatonin action on Leydig cells, (b) testicular expression of melatonergic receptors, and (c) possible interactions between melatonin receptors and the previously identified testicular serotoninergic and CRH (CRH) systems. In isolated Leydig cells from active testes of adult hamsters kept in a long-day (LD, 14/10 h light/dark) photoperiod, and from regressed testes of adult animals exposed to a short-day photoperiod during 16 weeks (16SD, 6/18 h light/dark), melatonin significantly reduced hCG-stimulated production of cAMP and the main androgens: testosterone and androstane-3,17-diol (3-Diol), respectively, and decreased the expression of Steroidogenic Acute Regulatory (StAR) protein, P450 side chain cleavage (P450scc), 3-hydroxysteroid dehydrogenase (3-HSD) and 17-hydroxysteroid dehydrogenase (17-HSD). In 16SD-Leydig cells, melatonin stimulated the conversion of testosterone into 5-reduced androgens by inducing 5-reductase isoform 1 (5-R1), and controlled 3-Diol production by inhibiting 3-hydroxysteroid dehydrogenase (3-HSD) expression. Mel1a receptors were detected in Leydig cells. While, the local serotonin system did not mediate melatonin action on androgen production, melatonergic effect on steroidogenesis involved the interaction between mel1a receptors and the inhibitory CRH system. Moreover, melatonin significantly increased CRH mRNA levels and production in hamster Leydig cells expressing CRH-R1 receptors.

Our studies indicate that melatonin may act as a local inhibitor of hCG-stimulated cAMP and androgen production through mel1a receptors, down-regulation of StAR and key steroidogenic enzymes expression, and its interaction with the local CRH system.