The anterior pituitary gland as a possible site of action of kainic acid.
The purpose of the present study was to analyze the direct effect of kainic acid (KA), an agonist of L-Glutamate, on the secretion of LH and FSH from anterior pituitary (AP) of male rats perifused in vitro. At low concentrations (1 microM), KA was able to stimulate the release of both gonadotropins from AP of 50-day-old male rats, but the response to subsequent stimuli was markedly impaired. This, however, was not due to a neurotoxic action of KA, but seemed rather suggestive of a down-regulation or desensitization of KA receptors. The stimulatory action of KA on LH and FSH secretion was age-dependent, since the agonist was completely ineffective on the AP of 75-day- and 18-month-old male rats. DNQX (6,7-dinitroquinoxaline-2,3-dione), a specific antagonist of the KA receptor subtype, was able to block the KA-induced gonadotropin secretion; similarly, AP-5 (2-amino-5-phosphonovalerate), a competitive NMDA receptor antagonist, prevented the stimulatory effect of KA on LH and FSH release. An interaction between the opiatergic and the excitatory aminoacid (EAA) systems emerged from the observation that pulses of KA applied to AP of 50-day-old male rats during a continuous perifusion with a medium containing morphine (5 microM) failed to increase gonadotropin secretion. These results indicate that KA can, at low concentrations, directly stimulate LH and FSH secretion by acting at AP level; this effect disappears with progression of age, and might be exerted both through NMDA and non-NMDA receptor subtypes. Finally, the results provide evidence that opioids and excitatory aminoacids might influence gonadotropin secretion from AP by acting in opposite directions.
Zanisi
M
M
Institute of Endocrinology, University of Milano, Italy.
Galbiati
M
M
Messi
E
E
Martini
L
L
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D005640:Follicle Stimulating Hormone / Q000378:metabolism*; D007608:Kainic Acid / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000378:metabolism*; D008297:Male; D009020:Morphine / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017459:Receptors, Amino Acid / Q000037:antagonists & inhibitors; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors
D015763:2-Amino-5-phosphonovalerate; D005640:Follicle Stimulating Hormone; D007608:Kainic Acid; D007986:Luteinizing Hormone; D009020:Morphine; D011810:Quinoxalines; D017459:Receptors, Amino Acid; D018092:Kainic Acid Receptors; C031959:aspartic acid receptor; C056723:FG 9041