Quinolinic acid stimulates luteinizing hormone secretion in female rats: evidence for involvement of N-methyl-D-aspartate-preferring receptors.
Pharmacological evidence suggests that endogenous excitatory amino acid neurotransmitters stimulate luteinizing hormone (LH) secretion in neonatal and adult rats. Recent studies have identified quinolinic acid (QUIN), an endogenous brain and peripheral metabolite of tryptophan, as a potent agonist at N-methyl-D-aspartate (NMDA)-preferring excitatory amino acid receptors. The present studies examined whether QUIN alters LH secretion in ovariectomized, estradiol-primed rats and whether such effects are mediated by specific amino acid receptor subtypes. In one experiment, animals received intracisternal injections of either quinolinic acid, N-methyl-DL-aspartate (NMA), aspartate (ASP), quisqualic acid (QA), or monosodium glutamate (GLU) five minutes prior to decapitation. In a second study, animals receiving central QUIN or NMA were treated simultaneously with either 2-amino-7-phosphonoheptanoic acid (APH) or kynurenic acid (KYA), both antagonists of NMDA-preferring receptors, or the quisqualate antagonist, glutamate diethyl ester (GDEE). Serum LH concentrations were measured by radioimmunoassay. Intracisternal administration of either QUIN or NMA resulted in an acute, dose-dependent increase of serum LH concentrations. Coadministration of APH blocked the effects of QUIN and NMA. QUIN stimulation of LH was also blocked by KYA, but not GDEE. Neither GLU nor ASP increased LH release, but QA did produce a small, significant elevation of LH. Light microscopic evaluation of brains showed no morphologic disturbance resulting from administration of these agents. The present results suggest that QUIN, or other endogenous ligands of NMDA-preferring receptors, may participate in the regulation of LH secretion in the adult female rat.
Johnson
M D
MD
Whetsell
W O
WO
Crowley
W R
WR
D000818:Animals; D005260:Female; D007986:Luteinizing Hormone / Q000378:metabolism*; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology*; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects*
D011725:Pyridines; D011805:Quinolinic Acids; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D007986:Luteinizing Hormone; D017378:Quinolinic Acid