Dihydrotestosterone is the active androgen in the maintenance of nitric oxide-mediated penile erection in the rat

Abstract

Androgens are essential for the expression of normal libido in the male, but their role in the maintenance of the erectile response in humans is controversial. It has been shown previously in the rat that castration induces 1) loss of penile reflexes; and 2) considerable reduction in the erectile response to electric field stimulation (EFS) of the cavernosal nerve. Both of these effects can be reversed by testosterone replacement. The current study was performed to determine whether these testosterone effects are mediated via its conversion to dihydrotestosterone (DHT), and to what extent the synthesis of the mediator of penile erection, nitric oxide, is affected by castration and androgen replacement. Five-month-old rats were either castrated or left intact. The orchiectomized rats were implanted with SILASTIC brand silicon tubing (Dow Corning) containing testosterone or DHT with or without daily injections of the 5 alpha-reductase inhibitor finasteride. After 7 days, rats were submitted to EFS and the intracavernosal pressure was recorded. Castration reduced the EFS-induced erectile response by 50% in comparison with intact rats and testosterone restored this decrease to normal. When finasteride was given to these testosterone-treated castrate rats, erectile response was not restored. DHT was as effective as testosterone in restoring response to EFS in castrates and this effect 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 failure seen in castrated rats, and suggest that this effect may be mediated, at least partially, by changes in nitric oxide synthase levels in the penis.

Effects of Estrogen in the Male Rat Medial Amygdala: Infusion of an Aromatase Inhibitor Lowers Mating and Bovine Serum Albumin-Conjugated Estradiol Implants Do Not Promote Mating

“…DHT capsules of this size have been reported to produce circulating DHT levels in the physiological range [41,42,43] and were behaviorally effective in another study in which we used identical DHT capsules s.c. and found that mating occurred if male rats were given either E 2 or BSA-E 2 implants to the MPO, whereas DHT-treated males with vehicle MPO implants did not mate [44]. Thereafter, they were stereotaxically implanted bilaterally with 22-gauge stainless steel, ethylene oxide sterilized guide cannulae (Plastics One) aimed at the MEA (level skull coordinates: AP = –3.2 mm, ML = ± 3.5 mm, DV = –8.2 mm [39]).…”

The Dark Side of 5α-Reductase Inhibitors' Therapy: Sexual Dysfunction, High Gleason Grade Prostate Cancer and Depression

“…Administration of 5α-DHT with or without the 5α-RIs, 17βTC, restored sexual behavior in long-term castrated male rats and mice suggesting a critical role for 5α-DHT in erectile physiology [29]. Further animal studies showed castration resulted in 50% reduction in erectile response, which was reversed by T treatment [30]. However, treatment with T together with finasteride did not restore the erectile response in castrated animals, suggesting that 5α-DHT is an important hormone in erectile physiology.…”

Implants of Estradiol Conjugated to Bovine Serum Albumin in the Male Rat Medial Preoptic Area Promote Copulatory Behavior

“…DHT capsules of this size have been reported to produce circulating DHT levels in the physiological range [41,42,43]. Thereafter, they were stereotaxically implanted bilaterally with 22-gauge stainless-steel, ethylene oxide-sterilized, guide cannulae (Plastics One, Roanoke, Va., USA) aimed at the MPO (level skull coordinates: anterior-posterior = –0.5 mm, medial lateral = ± 0.75 mm, dorsal-ventral = –8.0 mm [44]).…”