DIHYDROTESTOSTERONE IS THE ACTIVE ANDROGEN IN THE MAINTENANCE OF NITRIC OXIDE-MEDIATED PENILE ERECTION IN THE RAT

Androgens are essential for the expression of normal libido in the mal e, but their role in the maintenance of the erectile response in human s is controversial. It has been shown previously in the rat that castr ation induces 1) loss of penile reflexes; and 2) considerable reductio n in the erectile response to electric field stimulation (EFS) of the cavernosal nerve. Both of these effects can be reversed by testosteron e replacement. The current study was performed to determine whether th ese testosterone effects are mediated via its conversion to dihydrotes tosterone (DHT), and to what extent the synthesis of the mediator of p enile erection, nitric oxide, is affected by castration and androgen r eplacement. Five-month-old rats were either castrated or left intact. The orchiectomized rats were implanted with SILASTIC brand silicon tub ing (Dow Corning) containing testosterone or DHT with or without daily injections of the 5 alpha-reductase inhibitor finasteride. After 7 da ys, rats were submitted to EFS and the intracavernosal pressure was re corded. Castration reduced the EFS-induced erectile response by 50% in comparison with intact rats and testosterone restored this decrease t o normal. When finasteride was given to these testosterone-treated cas trate rats, erectile response was not restored. DHT was as effective a s testosterone in restoring response to EFS in castrates and this effe ct was not decreased by finasteride. Nitric oxide synthase activity in the penile cytosol was measured by the arginine-citrulline conversion and was found to correlate with the EFS determinations. These results show that DHT is the active androgen in the prevention of erectile fa ilure seen in castrated rats, and suggest that this effect may be medi ated, at least partially, by changes in nitric oxide synthase levels i n the penis.