Intratesticular factors controlling testicular function.

Abstract

Although the testis is under overall control by pituitary gonadotropins, intratesticular control mechanisms are important 1) because of the unique structural organization of the testis, and 2) because of the organization and local requirements of spermatogenesis. The avascular nature of the seminiferous tubules, which comprise 90% of testicular mass in most mammals, means that their exceptionally high energy and nutritional demand has to be met by local transport in testicular interstitial fluid (IF). The rate of formation of IF is determined by capillary permeability and local control of this process is thus a prerequisite for ensuring full nutritional and hormonal support for spermatogenesis. The latter is organized into specific stages arranged in a cycle, each stage having different requirements which only local control mechanisms can ensure. In the rat, Stage VII of the spermatogenic cycle has an absolute requirement for high levels of testosterone and maintenance of such levels in the testicular IF surrounding the tubules thus constitutes a crucially important function requiring local control. Because in this situation, testosterone works via the Sertoli cell and because the testosterone is produced locally by the Leydig cells in response to luteinizing hormone (LH), it is suggested that local control of intratesticular levels of testosterone is likely to be effected by a factor (or factors) produced by the Sertoli cell which acts on the Leydig cell, and which interacts with LH to modulate the levels of testosterone in testicular IF. The possibility that "testicular luteinizing hormone releasing hormone (LHRH)" may fulfill this role is examined in detail by investigating the local effects of an LHRH agonist (LHRH-A) on testicular capillary permeability and the IF levels of testosterone in normal intact adult rats. The results show that LHRH-A has dose-dependent effects on capillary permeability and the IF levels of testosterone and that these effects are modulated according to the ambient level of LH. Alteration of the IF levels of testosterone by LHRH-A is shown to be biologically effective and to be mediated partly by direct effects on Leydig cell steroidogenesis and partly by the control of capillary permeability. The physiological implications and operation of this local mechanism are discussed.