SITES OF HORMONE PRODUCTION IN THE MAMMALIAN TESTIS, AND THEIR SIGNIFICANCE IN THE CONTROL OF MALE FERTILITY

Abstract

The purpose of this paper is to summarize the evidence that there are 2 main lines of hormone production in the testis to discuss the relationship between the 2 systems and to show how the available information could be of practical value in achieving a suitable method of fertility control. In a wide variety of mammals including man a mass of cytoplasm or residual body is shed by each germ cell just before it passes down the seminiferous tubule. This material is phagocytosed by the Sertoli cells by an increase in lipid content. This lipid wanes as spermatogenesis proceeds to a low level after meiosis has been completed and the cycle is repeated as each generation of spermatids attains maturity. The administration of FSH causes a reduction in the lipid/sterol content of the Sertoli cells of estrogen-treated rats. It is ineffective when the germinal epithelium has been destroyed. The absence of some releasing factor from the germ cells is assumed. Morphological evidence endorses the view that the stereogenetic activity of the tubules is due to the Sertoli cells. In view of the evidence it is the androgens elaborated by the Sertoli cells that are responsible for the normal maintenance of spermatogenesis. This effect is related to the androgenicity of the compounds of which testosterone is probably the most important. Maintenance of the secondary sex characteristics under normal conditions is by the Leydig cells. When FSH is administered to estrogen-treated rats the large amount of lipid/cholesterol present in the Sertoli cells is metabolized and spermatogenesis is restored. Androgen production by the Sertoli cells seems to be governed by the availability of FSH. A way to control spermatogenesis without affecting secondary sex characteristics may be to use an agent that inhibits the production or activity of either FSH or the tubular androgens. Creating an autoimmune reaction would not be readily reversible. Also the secondary sex characteristics would be affected. Use of an oral androgen at a dose level sufficient to depress the level of FSH and maintain the secondary sex characteristics but too low to stimulate the germinal epithelium would achieve fertility control in man. Most oral androgens available appear to be C-17-alklated derivatives of testosterone and androstenediol which are liable to produce impairment of hepatic function. Mesterolone lacks this C-17-alkyl group. In animal experiements the size of the testicles is reduced by estrogen-androgen administration (depending on dosage employed) but there is an increase in libido. Thus there may be developed the male equivalent of the female pill as an oral contraceptive.