Interactions Between Androgens, Sertoli Cells and Germ Cells in the Control of Spermatogenesis

Abstract

One of the major unanswered questions in andrology is ‘How does testosterone control spermatogenesis?’ As testosterone is all-important for maintenance of spermatogenesis in all species of mammals that have been studied, answering this question is likely to give us major insight into the basic mechanisms involved in the control of spermatogenesis. Four years ago we initiated a major programme of work which sought to determine to the molecular level how testosterone controlled spermatogenesis. This paper summarizes the results of these studies including the surprises, the disappointments and the achievements. The first important decision we took was deciding how to answer the question. A survey of the literature (reviewed in Sharpe 1994) made it plain that testosterone appeared to exert little, if any, effect on the function of isolated Sertoli cells, irrespective of whether these were isolated from immature (15–21 days of age) or adult (hypophysectomized) rats. We chose to interpret this lack of information as evidence that these studies had used inappropriate approaches to answering the question, a decision which has proved to be 100% correct (not all of our thinking has turned out to be so accurate!). The available data shows clearly that Sertoli cells from immature rats are primarily follicle-stimulating hormone (FSH)- rather than testosterone-responsive, so the absence of any well-described effects of testosterone in this situation was predictable (Sharpe 1994). Where Sertoli cells had been isolated from adult rats, the latter had been hypophysectomized 3 or more weeks earlier so as to facilitate Sertoli cell isolation (by removal of most of the germ cells) as well as inducing major testosterone-withdrawal. In light of the growing evidence for germ cell modulation of Sertoli cell function (reviewed in Jégou 1993 and Sharpe 1993), we concluded that perhaps a normal germ cell complement was required for testosterone to act on the Sertoli cells — another conclusion that we have since proved to be correct.