A report prepared for the ford foundation review of research and support in reproductive biology and contraceptive development

Abstract

This report, prepared for the Ford Foundation, reviews research and supported studies of male reproductive biology and contraception during the past 10 years. Since future research in male contraception must determine whether interrupted spermatogenesis is compatible with persistent normal Leydig cell function, the issue hinges on possible involvement of Leydig cells in the feedback control of spermatogenesis. The Leydig cells have been shown to be the major source of testicular androgen. The action of testosterone on target cells in the testes and elsewhere brings about the aspects of maleness. Germinal epithelium has a higher testosterone requirement than other androgen target tissues. The Sertoli cells of the seminiferous tubules are believed to have little or no capability of de novo steroid biosynthesis. Spermatogenesis is dependent on high testosterone concentration in the immediate vicinity. Mitochondria of Leydig cells have been associated with conversion of cholesterol to pregnenolone, a step in biosynthesis of testosterone, and there seems to be a progression from pregnenolone through progesterone to testosterone. Increased testosterone secretion follows luteinizing hormone (LH) administration within 15 minutes, both in vivo and in vitro, apparently because LH stimualtes biosynthesis by accelerating the first step in cholesterol side-chain cleavage. This LH action is confined to testicular Leydig cells. Some experiments suggest that adult Leydig cells are not maximally stimulated by endogenous gonadotropin. Continuing treatment with exogenous gonadotropin increases plasma testosterone levels and causes changes in Leydig cells but LH seems necessary to maintain testosterone production by the Leydig cells. Follicle stimulating hormone acts specifically only on seminiferous tubules. However, antispermatogenic contraception strategies may affect normal Leydig cell function. A major concern of hormonal male contraception will be the extent to which secondary effects of Leydig cell function are preserved. Exogenous testosterone must be able to substitute adequately. Agents that interrupt spermatogenesis have also adversely affected Leydig cells. Vasectomy may prove more promising as Leydig cells have shown no resulting morphologic changes. Oral administration of progestin combined with sc testosterone implants have achieved cessation of spermatogenesis without elevation of plasma testosterone. Testicular shrinkage from spermatogenesis suppression can be concealed by Silastic prosthesis. Major gaps still remain in knowledge.