The overall objective of this project is to evaluate the biochemical and morphological response of the testis and epididymis to a withdrawal or deprivation of FSH. The effects of treatment with inhibin on first wave of spermatogenesis in the immature rat as well as on spermatogenesis and fertility in the rat and monkey will be investigated. Levels of inhibin, Androgen Binding Protein (ABP), Testosterone, and DHT in the testis and epididymis will be measured in these animals. Circulating levels of gonadotropins, inhibin and androgens will be measured. Site of production of inhibin in rat and bovine Sertoli cells in culture and in bovine testis will be localized by electron microscopic immunocytochemical techniques. The effects of active immunization with FSH--subunit on the male crab-eating monkey (M. fasicularis) will be investigated, using the following parameters to monitor: a) changes in testicular morphology using light and electron microscopic techniques, b) semen analysis, including sperm count, motility, structure, levels of inhibin, and androgens, c) ABP levels in the testis and epididymis and d) peripheral levels of androgens, LH and any free residual FSH. The inhibin levels will be measured using radioimmunoassay and radioreceptor assay. The peripheral antibody titres in the plasma of the immunized monkeys will be correlated with the above parameters during the progress of immunization. Inhibin-FSH-Testosterone interrelations will be explored using antigonadotropic sera, and hypophysectomy in the rat and the monkey. These studies are of potential importance to a better understanding of the role of FSH in male reproduction. The proposed studies in inhibin will, in addition, provide new and significant information on the modulation of FSH secretion. These approaches hold the promise of providing effective means for pharmacologic blockade of FSH for both basic research and possible applications.
