PMID- 12694377 OWN - NLM STAT- MEDLINE DCOM- 20030807 LR - 20190922 IS - 0953-8194 (Print) IS - 0953-8194 (Linking) VI - 15 IP - 5 DP - 2003 May TI - 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. PG - 516-20 AB - 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. FAU - Gao, C-Q AU - Gao CQ AD - Department of Endocrinology and Heymans Institute of Pharmacology, Ghent University, Ghent, Belgium. FAU - Kaufman, J-M AU - Kaufman JM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neuroendocrinol JT - Journal of neuroendocrinology JID - 8913461 RN - 0 (Receptors, LHRH) RN - 33515-09-2 (Gonadotropin-Releasing Hormone) RN - 6384-92-5 (N-Methylaspartate) RN - 76326-31-3 (2-amino-5-phosphopentanoic acid) RN - 9002-67-9 (Luteinizing Hormone) RN - HG18B9YRS7 (Valine) RN - OON1HFZ4BA (cetrorelix) SB - IM MH - Animals MH - Gonadotropin-Releasing Hormone/analogs & derivatives/pharmacology MH - Guinea Pigs MH - Luteinizing Hormone/blood/*metabolism MH - Male MH - N-Methylaspartate/*pharmacology MH - Receptors, LHRH/*antagonists & inhibitors/physiology MH - Valine/*analogs & derivatives/pharmacology EDAT- 2003/04/16 05:00 MHDA- 2003/08/09 05:00 CRDT- 2003/04/16 05:00 PHST- 2003/04/16 05:00 [pubmed] PHST- 2003/08/09 05:00 [medline] PHST- 2003/04/16 05:00 [entrez] AID - 1024 [pii] AID - 10.1046/j.1365-2826.2003.01024.x [doi] PST - ppublish SO - J Neuroendocrinol. 2003 May;15(5):516-20. doi: 10.1046/j.1365-2826.2003.01024.x.