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 microg or 10 microg) 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.
Gao
C-Q
CQ
Department of Endocrinology and Heymans Institute of Pharmacology, Ghent University, Ghent, Belgium.
Kaufman
J-M
JM
D000818:Animals; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology; D006168:Guinea Pigs; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism*; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D011966:Receptors, LHRH / Q000037:antagonists & inhibitors* / Q000502:physiology; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology
D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; D016202:N-Methylaspartate; C056639:2-amino-5-phosphopentanoic acid; D007986:Luteinizing Hormone; D014633:Valine; C062876:cetrorelix