Melatonin participates in the control of testosterone secretion from rat testis: an overview of our experience

The androgen milieu plays an important role in the control of immunity, and melatonin (MLT) is known to modulate the immune response as well. Our recent studies have focused on the role of MLT in controlling androgen secretion from rat testis. The presence of MLT receptors, their modulation, and the effect of MLT on steroidogenesis have been studied on Percoll-purified rat Leydig cells (LCs) cultured in vitro. MLT receptors present in adult rat LCs (B(max) = 46.7 +/- 3.5 fmol/mg protein; K(d) = 88.7 +/- 6.2 pmol/l) are coupled through a pertussis toxin-sensitive G-protein and are downregulated by prolonged exposure to MLT itself. When acutely added for three hours, MLT (0.4-400 nM) inhibits T secretion in response to LH, forskolin, and GnRH, but sensitizes cAMP-dependent T secretion when present in the preincubation media (16 h). The acute inhibition of adenylyl cyclase and the block of 17-20-desmolase (with increased 17-OH-progesterone) and of calcium release from the intracellular stores, followed by sensitization of the adenylyl cyclase activity in the long term, are described as mechanisms of MLT action. Ultimately, our studies suggest that MLT is likely to control the immune response not only through its direct effects, but also by finely modulating the androgen milieu.