The two primary functions of the adult testis (sperm production and hormone production) need to be co-ordinated because sperm production is completely dependent on appropriate hormone (primarily testosterone) production. However, it is equally evident from animal studies that Leydig cell (LC) development and function are also affected by developmental and functional status of the seminiferous tubules. For example, development of the adult LC population is dependent on reduced secretion of anti-Müllerian hormone (AMH) from the Sertoli cells. Similarly, the rate and location of regenerating adult LC in the rat, after their destruction by administration of the toxicant ethane dimethane sulphonate (EDS), is critically dependent on the germ cell complement of the neighbouring seminiferous tubules. This also fits with evidence from the human for a high incidence of compensated LC failure in men with infertility/low sperm counts.
It is also established in animal studies that androgens themselves play a role in development of the adult LC. This has been highlighted by the demonstration that androgen-receptor (AR)-knockout mice (ARKOs) exhibit an ∼80% reduction in LC number in adulthood. Although this may result from loss of androgen action directly on the LC, Sertoli cell-selective knockout of the AR (SCARKOs) also results in ∼50% reduction in LC number, indicating that androgen action on Sertoli cells is also important for adult LC development; altered action of oestrogens and/or platelet-derived growth factor are likely explanations for the reduced LC number in SCARKOs.
Finally, there is growing evidence that the stem cells for adult LC may have their origins in fetal life and that altered androgen action during this period might permanently alter LC number and/or function in adulthood. This is being explored by investigating development of adult LC after experimental manipulation of fetal testicular testosterone levels/action in the rat.
06 - 07 Nov 2006
Society for Endocrinology