5α-Reduced androgens and testicular function in the immature rat: Effects of 5α-androstan-1 7β-ol-3one (DHT) propionate and 5α-androstan-3α,17β-diol

Increasing doses of dihydrotestosterone propionate (DHTP) and 5α-androstan-3α,17β-diol (ADIOL) were given to 21-day-old rats for 10 days. Various parameters of reproductive function were assessed including testis weight, epididymal androgen binding protein (ABP) (Sertoli cell activity), plasma LH and FSH and the testicular levels of androstenedione (A), testosterone (T), dihydrotestosterone (DHT) and 5α-androstan-3α,17β-diol (ADIOL).In the control population, of the androgens measured, only the testicular concentration of DHT was highly correlated with epididymal ABP levels.After treatment with varying doses of DHTP, testis weight and epididymal ABP exhibited a biphasic response with maximum suppression occurring at the 100–250gmg/day dose level. Recovery of both of these parameters to control levels with 5,000–10,000 μg/day DHTP was associated with an increase in testicular DHT to normal or Supranormal levels. Plasma LH and FSH (pituitary function) and testicular A and T (Leydig cell function) were suppressed in a dose-dependent manner at doses including and higher than 50 μg DHTP/day. The testicular content of ADIOL was returned to control levels with 500 μg DHTP/day, when Sertoli cell function and spermatogenesis were still markedly suppressed. At DHTP doseshigher than 500 Jug/day, ADIOL was the predominant intratesticular androgen.Treatment with ADIOL also evoked a biphasic response from testis weight and epididymal ABP comparable to that observed with DHTP and testosterone propionate (TP) (Weddington et al., 1976). Doses from 20–500 μg/day resulted in a gradual, dose-dependent suppression of all the parameters studied. Administration of 1000 μg/day ADIOL returned the testicular ADIOL content to the control level. At the same dose, epididymal ABP, testis weight and the other intratesticular androgens were still maximally suppressed. Doses of 5000 and 10,000 μg/day ADIOL elevated the endogenous ADIOL in the testis to 4 and 25 times the normal level respectively. These higher doses also caused a dose-dependent increase in intratesticular DHT which was paralleled by an increase in epididymal ABP and testis weight. Even at the highest dose of ADIOL injected, DHT, epididymal ABP and testis weight did not completely return to normal levels.It is concluded that the previously observed stimulation of Sertoli cell function and spermatogenesis by androgens, in the rat, is mediated through DHT. Furthermore, the findings indicate that the apparent direct stimulation of Sertoli cell function by ADIOL is mediated through its conversion to DHT. The sensitivity of the testis to various androgens cannot be clearly interpreted on the basis of the administered doses, but only in relation to the levels of endogenous androgens in the testis achieved by the hormone treatment. In this regard, the study emphasizes the need for careful interpretation of data involving androgen treatment, especially ADIOL, and suggests that the relative potency of androgens in a bioassay system does not necessarily provide clear information about their relative potency at the target cell level.