131 MELATONIN–INDUCED INHIBITION OF SEXUAL MATURATION IN THE MALE RAT: EVIDENCE FOR CENTRAL INHIBITION OF GnRH SECRETION

Abstract

We have shown that daily treatment with melatonin (MT) markedly delays sexual maturation in the male rat. The observations that MT-treated rats have normal pituitary responsiveness to GnRH and low or absent pulsatile release of LH pointed out for a central inhibitory action of MT on GnRH release. The sensitivity of MT-treated rats to gonadectomy and sex steroid replacement was investigated: male rats receiving 100 μg MT daily or saline were castrated at 30 d and immediately treated with various doses of testosterone propionate (T), or oil until sacrifice at 40 d. In animals that received oil, LH release was drastically reduced in MT-treated rats (46.0±7.3 ng/ml) as compared to controls (305±44) demonstrating that MT inhibits GnRH secretion in absence of sex steroid. Replacement with T showed that MT-treated rats were much more sensitive to T than controls, suggesting that MT potentiates the ⊝ feed-back action of T on LH release. Conversely, the ability of GnRH neurons of MT-treated rats to release GnRH in response to N-methyl-DL-aspartic acid (NMA), an excitatory amino acid analog known to cause LH release via GnRH, was found normal at 30 d since NMA (20 mg/kg BW, iv) elicited the same LH response in MT-treated and in control rats. These data further indicate that MT induces central inhibition of GnRH release without impairing secretory processes of GnRH neurons and prolongs the high sensitivity to sex steroid ⊝ feed-back typical of infantile animals.