SEXUAL DIFFERENCES IN THE ROLE OF KAINATE RECEPTORS IN CONTROLLING GONADOTROPIN-SECRETION IN PREPUBERTAL RATS

Glutamate stimulates LH secretion in adult female rats after activatio n of N-methyl-D-aspartic acid (NMDA), kainate, and 2-amino-3-hydroxy-5 -methyl-4-isoxazol propionic acid receptors. In contrast to the positi ve role of kainate receptors in the control of LH secretion in adult f emales, neither activation nor antagonization of kainate receptors in immature rats modified the onset of puberty. The present experiments w ere carried out to establish why, if kainate stimulates LH release in adult rats, it fails to advance puberty in immature rats, and to deter mine whether the role of kainate receptors is sexually dimorphic aroun d puberty. In Expt 1, 4-, 8-, 12-, 16-, 20- and 30-day-old females wer e investigated 15 min after administration of vehicle or kainic acid, a kainate receptor agonist (2.5 mg kg(-1)). In Expt 2, 30-day-old fema le rats were studied 2, 5 and 10 min after administration of vehicle, 2.5 mg kainic acid kg(-1) or NMDA, an NMDA receptor agonist (15 mg kg( -1)). In Expt 3, female and male rats were gonadectomized or sham-gona dectomized on day 23 and investigated on day 30 after injection of veh icle, kainic acid (2.5 mg kg(-1) at -15 min) or 6,7 dinitroquinoxaline -2,3 dione (DNQX), a kainate antagonist (2 mg kg(-1) in two injections at -120 and -60 min). Finally, 30-day-old female and male rats were i nvestigated 15 min after injection of vehicle or NMDA (15 mg kg(-1)) o r 60 min after administration of different doses of 0,11-dihydro-5H-di benzo[a,d]cyclohepten-5,10-imine (MK-801), an NMDA antagonist (0.1, 0. 25 or 0.50 mg kg(-1)). The results indicate that the role of kainate r eceptors in the control of gonadotrophin secretion is sexually dimorph ic around puberty, since: (a) LH secretion was stimulated by kainic ac id in male rats but inhibited in females; (b) FSH secretion was inhibi ted by kainic acid in ovariectomized females, but not in orchidectomiz ed males; and (c) DNQX inhibited LH secretion in males but not in fema les. These differences were specific for kainate receptors since, in b oth sexes, NMDA stimulated and MK-801 inhibited LH secretion. It may b e concluded that the secretion of gonadotrophins is modulated differen tly by kainate receptors in prepubertal male and female rats.