Intratesticular factors and testosterone secretion: the effect of treatment with ethane dimethanesulphonate (EDS) and the induction of seminiferous tubule damage.

The role of seminiferous tubule dysfunction in regulating the levels of a factor (or factors) in testicular interstitial fluid (IF) which stimulates Leydig cell testosterone secretion in vitro, was assessed by injecting rats with the Leydig cell toxin, EDS. Within 72 h of treatment EDS destroyed the Leydig cells and concomitantly reduced IF testosterone to undetectable levels. This was associated with nearly a 2-fold increase (P less than 0.001) in levels of the IF-factor(s) as judged by the enhancement of hCG-stimulated testosterone production (= IF bioactivity). By 3 weeks, and thereafter up to 10 weeks post-EDS, Leydig cells regenerated within the testis, and testosterone levels returned to control values, but IF-bioactivity remained significantly increased. The latter was associated with seminiferous tubule dysfunction as indicated initially by testicular morphology, raised serum levels of FSH and reduced testicular weight. For animals with normal testosterone levels, there was a significant negative correlation (r = -0.57, N = 46; P less than 0.001) between testicular weight and IF bioactivity. A similar increase in IF bioactivity in the presence of normal testosterone levels was observed in rats in which patchy severe seminiferous tubule damage had been induced by short-term cryptorchidism. It is concluded that, in addition to testosterone, seminiferous tubule function may dictate the intratesticular levels of the testosterone-stimulating factor(s) in IF.