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 resp onse to electrical field stimulation (EFS) of the cavernosal nerve, an d the activity of penile nitric oxide synthase (NOS). Both changes are prevented by androgen administration. We have now investigated whethe r other strategies of androgen ablation or competition may act as stro nger inhibitors, and, if so, whether the stronger inhibition is due to the depletion of penile NOS content. Rats were castrated or left inta ct 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 silas tic tubing, s.c.). Additional groups of intact rats received injection s of a GnRH antagonist (GnRHA, 1.25 mg/kg, s.c.), or were hypophysecto mized and left untreated. Controls were untreated intact and castrated animals. After 7 days, rats were subjected to EFS, and the ratios bet ween 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 red uced the MIP:MAP ratio and penile NOS activity. Androgen receptor bloc kade with flutamide induced a similar response in intact rats. When fl utamide treatment was combined with castration, the erectile response was nearly abolished, but NOS activity was not decreased below the val ues in castrated rats. Estradiol given to castrated rats and hypophyse ctomy or GnRHA treatment in intact rats diminished the erectile respon se below the level in castrated animals. In hypophysectomized rats, pe nile NOS activity fell below levels in castrated animals. Contents of nNOS and eNOS were not significantly reduced by any treatment. These d ata suggest that penile erection in the rat is completely dependent on androgens, presumably because of their role in the maintenance of pen ile NOS activity and of other ancillary factors. However, only the com plete blockade of residual androgen effects at the tissue level or a t otal androgen depletion can abolish the erectile response.