Daily afternoon administration of melatonin does not irreversibly inhibit sexual maturation in the male rat.

Previous studies from our laboratory demonstrated that daily afternoon melatonin injections from 20-40 days of age inhibited sexual development of young male rats, whereas in adult animals, similar injections had no effect. The present study was designed to determine more precisely the critical age period during which melatonin exerts its inhibiting effect and to see whether spontaneous sexual maturation resumes after discontinuation of melatonin administration at 45 days of age or even during continuous administration of melatonin until 115 days of age. Sexual maturation was evaluated using weights of seminal vesicles and testes; plasma levels of testosterone, FSH, and LH; pituitary contents and concentrations of FSH and LH; and, finally, pituitary content of GnRH receptors. Administration of melatonin to young male rats from 20-30 days of life had the same inhibitory effect on sexual maturation at 40 days as melatonin injections from 20-40 days. In contrast, administration of melatonin from 30-40 days only slightly decreased plasma testosterone concentration, weight of seminal vesicles, and pituitary GnRH receptor content. Melatonin administration from 38-40 days had no effect. Daily melatonin administration from 20-45 days of age was followed by resumption of sexual maturation, as observed at 70 days. The recovery was complete by 80 days of age when all of the parameters studied reflected complete sexual maturation. Finally, in rats treated continuously with melatonin from days 20 until 115, sexual maturation occurred but was delayed by about 20-30 days. Beginning of sexual development was observed at 60 days of life, and full development was attained only at 100 days. These data confirm that melatonin delays sexual maturation in the young male rat when administered daily in the afternoon. They demonstrate that this inhibitory action of melatonin is most critical between 20 and 30 days of life and is reversible regardless of whether melatonin administration is discontinued after 45 days of life. The suppression of the pubertal peaks of pituitary GnRH receptor number and pituitary and plasma FSH concentrations in treated rats suggests that melatonin interferes with the pubertal increase in GnRH secretion. In conclusion, these reversible effects of melatonin suggest that this pineal indolamine represents an important factor for the timing of sexual maturation.