Pituitary-gonadal function in neonatal and adult female rats treated with gonadotropin-releasing hormone agonist and antagonist: short- and long-term effects

Abstract

We have analyzed the mechanisms involved in ovarian failure after administration of gonadotropin hormone-releasing hormone agonists (GnRH-A) or antagonists (GnRH-ANT). Ovarian and uterine weights, serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol and pituitary FSH and LH contents were measured in Wistar female rats injected from 1–15 or 90–104 days of age with the agonist d-Ala6-d-Gly10-GnRH or the GnRH-ANT Org. 30276. Vaginal opening, first estrous presentation, vaginal smears and reproductive capacity were also analyzed. In both neonatal and adult females GnRH-A induced pituitary desensitization and reduced ovarian and uterine weights and estradiol serum concentrations. Therefore, serum gonadotropin concentrations were increased in adults and decreased in neonatal females. Puberty occurrence and reproductive function remain unaltered after neonatal treatment with GnRH-A. In neonatal females, FSH and LH pituitary content and FSH serum concentrations decreased at the end of treatment with GnRH-ANT. The effects on LH and estradiol secretion depended on the pattern of treatment. Interestingly enough, both vaginal opening and first estrous presentation were precipitated by GnRH-ANT administration. Normal reproductive function was observed in adults. We conclude that: (i) pituitary desensitization of receptors occurred in both neonatal and adult females after chronic administration of GnRH-A; (ii) the ovarian failure observed in adults that is accompanied by increased serum concentrations of gonadotropins was probably due to an inhibitory effect of GnRH-A directly on the ovaries; (iii) the blockade of GnRH action shortly after birth with GnRH-ANT precipitated the onset of puberty; possibly the antagonist blocks some suppressive effects of endogenous LHRH; (iv) the effects of neonatal administration of GnRH-A or GnRH-ANT were transitory.