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

Endocrinology. 1995 Apr;136(4):1495-501. doi: 10.1210/endo.136.4.7534702.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Oxidoreductases / metabolism
  • Animals
  • Dihydrotestosterone / pharmacology*
  • Electric Stimulation
  • Finasteride / pharmacology
  • Male
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase
  • Orchiectomy
  • Penile Erection / drug effects*
  • Penile Erection / physiology
  • Penis / enzymology
  • Rats
  • Rats, Inbred F344
  • Testosterone / pharmacology

Substances

  • Dihydrotestosterone
  • Nitric Oxide
  • Testosterone
  • Finasteride
  • Nitric Oxide Synthase
  • Amino Acid Oxidoreductases