The physiological regulation of 5 alpha-reductase (5 alpha R) as well as the complex pathogenesis of male and female androgenic disorders are still incompletely understood. Therefore, we examined the influence of various steroid hormones on the 5 alpha R activity in female and male genital skin fibroblasts in primary culture to test whether the 5 alpha R activity is identically regulated in genital skin samples of both sexes. Nine foreskin samples of male patients and 11 specimens of female genital skin were prepared and cultured as primary tissue cultures. After pre-incubation with various unlabeled steroids, [3H]-testosterone was added to the cultures and the 5 alpha R activity (conversion of testosterone to dihydrotestosterone) measured. (a) The pre-incubation of male foreskin fibroblasts with unlabeled androstenedione and androstandione both resulted in stimulation of 5 alpha R activity. Other unlabeled steroid hormones, including progesterone, testosterone, dihydrotestosterone, and estradiol had no significant effect on 5 alpha R activity. (b) In female genital skin fibroblasts, pre-incubation with testosterone also led to an increase in 5 alpha R activity, whereas pre-incubation with estradiol decreased 5 alpha R activity. None of the other unlabeled steroid hormones applied had significant effects. These data on male foreskin in culture suggest a physiologic regulatory mechanism of 5 alpha R activity independent of the concentration of the enzymatic substrate or product, whereas the results for the female genital skin suggest a cellular regulation of the androgen levels by the enzymatic substrate testosterone and a possible negative feedback mechanism of estrogens.(ABSTRACT TRUNCATED AT 250 WORDS)