Androgen and pituitary control of penile nitric oxide synthase and erectile function in the rat

Castration of adult male rats reduces by half the penile erectile response to electrical field stimulation (EFS) of the cavernosal nerve, and the activity of penile nitric oxide synthase (NOS). Both changes are prevented by androgen administration. We have now investigated whether other strategies of androgen ablation or competition may act as stronger inhibitors, and, if so, whether the stronger inhibition is due to the depletion of penile NOS content. Rats were castrated or left intact and were treated daily as follows: 1) intact, with the antiandrogen flutamide (25 mg/kg/day, i.p.); 2) castrated, with similar treatment; 3) castrated, with 17 beta-estradiol 3-benzoate (estradiol; via silastic tubing, s.c.). Additional groups of intact rats received injections of a GnRH antagonist (GnRHA, 1.25 mg/kg, s.c.), or were hypophysectomized and left untreated. Controls were untreated intact and castrated animals. After 7 days, rats were subjected to EFS, and the ratios between maximal intracavernosal pressure (MIP) and mean arterial pressure (MAP) were measured. Penile NOS activity and the contents of neuronal NOS (nNOS) and endothelial NOS (eNOS) were determined. Castration reduced the MIP:MAP ratio and penile NOS activity. Androgen receptor blockade with flutamide induced a similar response in intact rats. When flutamide treatment was combined with castration, the erectile response was nearly abolished, but NOS activity was not decreased below the values in castrated rats. Estradiol given to castrated rats and hypophysectomy or GnRHA treatment in intact rats diminished the erectile response below the level in castrated animals. In hypophysectomized rats, penile NOS activity fell below levels in castrated animals. Contents of nNOS and eNOS were not significantly reduced by any treatment. These data suggest that penile erection in the rat is completely dependent on androgens, presumably because of their role in the maintenance of penile NOS activity and of other ancillary factors. However, only the complete blockade of residual androgen effects at the tissue level or a total androgen depletion can abolish the erectile response.