Gonadal-Independent Developmental Changes in Activation of N-Methyl-D-Aspartate Receptors Involved in Gonadotropin-Releasing Hormone Secretion

Using hypothalamic explants of male rats, we have shown that the N-methyl-D-aspartate (NMDA) receptors involved in a stimulatory control of gonadotropin-releasing hormone (GnRH) secretion were transiently activated at 25 days around the time of onset of puberty. This was evidenced by studying the dose-related inhibition of veratridine-induced GnRH secretion by MK-801, a use dependent antagonist of NMDA receptors. An increase in sensitivity of GnRH secretion to the inhibitory effect of MK-801 was used as a marker of increased activation of NMDA receptors involved in stimulation of GnRH secretion. Here, we report on data obtained in intact and castrated rats at different ages. The aim was to determine whether the absence of gonads would affect the developmental changes in activation of NMDA receptors that we described recently. In pubertal (50-day-old) rats, orchidectomy resulted in an activation of NMDA receptors which was nonsignificant after 4 days but significant after 13 days. In prepubertal rats orchidectomized at 5 or 10 days and studied 10 days later, the NMDA receptors involved in GnRH secretion were also more activated than in intact animals. Using explants of intact and castrated animals, a similar increase in activation of NMDA receptors was observed between 15 and 25 days of age, a period preceding onset of puberty. Subsequently, between 25 and 50 days, a reduction in NMDA receptor activation was seen. This decrease was observed in intact rats showing normal sexual development and in castrated rats as well.(ABSTRACT TRUNCATED AT 250 WORDS)