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 k ainic 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 mu M), KA was able to stimulate the release of b oth 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-r egulation or desensitization of KA receptors. The stimulatory action o f 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 th e KA receptor subtype, was able to block the KA-induced gonadotropin s ecretion; similarly, AP-5 (2-amino-5 phosphonovalerate), a competitive NMDA receptor antagonist, prevented the stimulatory effect of KA on L H and FSH release. An interaction between the opiatergic and the excit atory aminoacid (EAA) systems emerged from the observation that pulses of KA applied to AP of 50-day-old male rats during a continuous perif usion with a medium containing morphine (5 mu M) failed to increase go nadotropin secretion. These results indicate that KA can, at low conce ntrations, directly stimulate LH and FSH secretion by acting at AP lev el; this effect disappears with progression of age, and might be exert ed both through NMDA and non-NMDA receptor subtypes. Finally, the resu lts provide evidence that opioids and excitatory aminoacids might infl uence gonadotropin secretion from AP by acting in opposite directions.