MECHANISMS OF REPRODUCTIVE DEFICIENCY IN MALE-RATS TREATED NEONATALLYWITH A GONADOTROPIN-RELEASING-HORMONE ANTAGONIST

It is well known that males injected neonatally with oestradiol or ant iserum or antagonists (ANT) against gonadotrophin-releasing hormone (G nRH) show multiple reproductive disorders. In the present work, in mal es treated neonatally with GnRH-ANT, we have analysed: (1) whether the impairment of reproductive function can be blocked by simultaneous tr eatment with gonadotrophins, (2) the possible differences in the effec ts of GnRH-ANT injected before or after the proliferation of Sertoli c ells which takes place between days 1 and 15 of age, and (3) the mecha nism(s) for the increased FSH secretion observed in adulthood. Experim ental designs included: administration of GnRH-ANT between days 1 and 16 or 15 and 30 of age, simultaneous administration of gonadotrophins and GnRH-ANT to neonatal males, and measurement of FSH secretion after orchidectomy or specific destruction of Leydig cells with ethylene di methane sulphonate (EDS) in adult males treated neonatally with GnRH-A NT. The principal new data presented in our studies are the following: (1) delayed puberty was observed not only in males injected neonatall y with GnRH-ANT, but also in those injected with gonadotrophins or wit h GnRH-ANT and gonadotrophins, (2) the decreased fertility and increas ed FSH secretion observed in adult males treated neonatally with GnRH- ANT were normalized by simultaneous administration of GnRH-ANT and gon adotrophins, and (3) the increased FSH secretion in adult males treate d neonatally with GnRH-ANT remained after EDS or orchidectomy, suggest ing that mechanisms other than decreased inhibin secretion were involv ed in the increased secretion of FSH.