Role of excitatory amino acid pathways in control of gonadotrophin secretion in adult female rats sterilized by neonatal administration of oestradiol or testosterone.

Abstract

Administration of sex steroids to neonatal female rats resulted in anovulation and absence of positive and negative feedback between oestradiol and LH secretion. In the present experiments, the role of excitatory amino acids in the control of gonadotrophin secretion in anovulatory adult rats sterilized by neonatal administration of oestradiol benzoate or testosterone propionate (100 mg or 1.25 mg on the day of birth, respectively) was studied. Cyclic females in metoestrus were used as controls. Serum LH and FSH concentrations were measured at different times after i.p. administration of N-methyl-D-aspartic acid (NMDA), kainic acid (agonists of NMDA and kainate receptors, respectively), MK-801 or 6,7-dinitroquinoxaline-2,3-dione (DNQX) (antagonists of NMDA and kainate receptors, respectively). Experiments were also performed in control and sterilized females 1 week after ovariectomy. It was found that: (1) the effectiveness of NMDA and kainic acid in stimulating LH secretion was significantly higher in sterilized than in cyclic females; (2) ovariectomy increased LH secretion only in control females; (3) the stimulatory effect of NMDA and kainic acid on LH secretion after ovariectomy was observed only in sterilized females; (4) MK-801 and DNQX selectively decreased LH secretion in sterilized females; and (5) FSH secretion remained unaffected after NMDA or kainic acid administration in both control and sterilized females. In conclusion, the results obtained in sterilized females showed both a tonic release of endogenous excitatory amino acids and a greater responsiveness to NMDA and kainic acid than in controls.