Stimulation of Luteinizing Hormone Secretion by N-Methyl-d,l-Aspartic Acid in the Adult Male Guinea-Pig: Incomplete Blockade by Gonadotropin-Releasing Hormone Receptor Antagonism

Stimulation of luteinizing hormone (LH) secretion by N‐methyl‐d,l‐aspartic acid (NMA), reported for several mammalian species, is generally accepted to be mediated through stimulation of hypothalamic gonadotropin‐releasing hormone (GnRH) release. In view of a previously reported unexpected inhibitory action of NMA on GnRH release from hypothalamic explant of intact male guinea‐pigs, the aim of the present study was to assess the in vivo effects of NMA in the adult male guinea‐pig. In the gonadally intact male, NMA (5 mg/animal) elicited a robust LH secretion, which was blocked by the N‐methyl‐d‐asparte‐receptor antagonist dl‐2‐amino‐5‐phosphonovaleric acid (AP‐5,12 mg/animal). In the castrated male, NMA elicited only a marginal and inconsistent LH secretion. Cetrorelix (CET), a GnRH receptor antagonist, administered intracardiacally 1 min or 45 min preceding bolus injection of NMA significantly reduced the LH response to NMA in the intact male. Surprisingly, following GnRH receptor blockade with CET, there still was a substantial residual serum LH response to NMA, while CET completely abolished the serum LH response to high dose (1 µg or 10 µg) guinea‐pig GnRH (gpGnRH). These results indicate that NMA stimulates LH secretion in the gonadally intact male guinea‐pig in vivo and that this effect is mediated in part through gpGnRH‐independent mechanisms.