INHIBITION OF 5-ALPHA-REDUCTASE ACTIVITY IMPAIRS THE TESTOSTERONE-DEPENDENT RESTORATION OF SPERMIOGENESIS IN ADULT-RATS

Testosterone (T) is required for spermatogenesis, particularly in the conversion of round spermatids between stages VII and VIII of spermato genesis. T is generally thought to be the major androgen involved in a dult spermatogenesis due to the high local concentration within the te stis, whereas its more potent 5 alpha-reduced metabolite dihydrotestos terone (DHT) is thought to be the active androgen in peripheral tissue s. The current study investigated whether 5 alpha-reduction of T to DH T is involved in the restoration of spermiogenesis in vivo in a settin g in which testicular T levels were markedly reduced. Adult male rats were given 3-cm T plus 0.4-cm estradiol implants for 9 weeks to suppre ss serum LH and testicular T levels and thereby inhibit spermatogenesi s. Increasing doses of T (3-, 6-, 10-, and 24-cm implants) were then g iven for 4 days to restore spermatogenesis in the presence or absence of a 5 alpha-reductase inhibitor (L685,273). The hourly production rat es of round spermatids in stages I-III, IV-VI, VII, and VIII were asse ssed using stereological techniques, and the conversion of round sperm atids between stages VII and VIII was then assessed as an index of and rogen action on spermiogenesis. Testicular androgen levels were measur ed by HPLC and RIA. The 5 alpha-reductase inhibitor significantly supp ressed (P < 0.05) the hourly production rate of round spermatids at th e 3- and 6-cm T doses, but not at the 10- and 24-cm doses. The convers ion of round spermatids between stages VII and VIII was suppressed (P < 0.05) by the inhibitor only at the 3- and 6-cm doses. The 5 alpha-re ductase inhibitor had no effect on testicular T levels, but suppressed (P < 0.05) DHT levels at the 6-, 10-, and 24-cm doses. We conclude th at the 5 alpha-reduction of T is involved in the restoration of spermi ogenesis at the lower administered doses of T and that these data are the first description of a role for 5 alpha-reduced androgens in adult spermatogenesis.