Control of gonadotropin secretion in prepubertal male rats by excitatory amino acids.

Abstract

The role of N-methyl-D-aspartate (NMDA) and non-NMDA receptors in the control of FSH and LH secretion was analysed in prepubertal male rats. In the first experiment 4, 8, 12, 16, 20 and 30-day-old males were decapitated 15 min after vehicle, NMDA or kainic acid (KA) administration. In the second experiment, 23-day-old males were sham-orchidectomized or orchidectomized. Orchidectomized males were or were not implanted with silastic capsules containing testosterone and were sacrificed on day 30 after injection with vehicle, NMDA (15 mg kg-1), LHRH (100 ng rat-1), NMDA plus LHRH, or MK801, a non-competitive NMDA antagonist, (1 mg kg-1). In the third experiment, 30-day-old intact males pretreated with Nw-nitro-L-arginine methyl ester (NAME) or NG-methyl-L-arginine (MA), blockers of nitric oxide (NO) synthase, were sacrificed after NMDA or KA administration. In the fourth experiment, the effects of NMDA, KA, LHRH and NAME were analysed in monolayer cultures of dispersed adenohypophyseal cells. We found that: (i) NMDA and KA stimulated LH and FSH secretion in intact males; (ii) the NMDA effect on LH secretion remained after orchidectomy; (iii) FSH and LH responses to LHRH were not affected by simultaneous NMDA administration; (iv) antagonization of NMDA receptors with MK801 reduced the LH secretion in intact and orchidectomized males and blunted the FSH response to orchidectomy; (v) the stimulatory effect of NMDA or KA on LH secretion was not affected by pretreatment with blockers of NO synthase; (vi) the in vitro LH secretion remained unchanged after administration of NMDA, KA or NAME. We conclude that NMDA and non-NMDA receptors play a physiological role in the control of the basal and post-orchidectomy secretion of gonadotropins, and that this effects is independent of changes in NO generation and does not include changes in pituitary responsiveness to LHRH.