The conversion of testosterone to 5α-androstan-17β-ol-3-one by expiants of human skin

The conversion of testosterone-1,2-³ H to dihydrotestosterone by slices of human skin obtained from various anatomical sites in a hundred and twelve normal subjects and three individuals with the syndrome of testicular feminization has been measured under standardized conditions utilizing thin-layer and gas-liquid chromatographic techniques. The rate of this reaction was found to be proportional to added substrate concentration up to 10^-6M testosterone, to be proportional to the weight of tissue slices up to 150 mg, and to be linear with time up to 3 hours. Very low rates of dihydrotestosterone formation were observed in sites obtained from the mons or from miscellaneous areas of the trunk and limbs of the control subjects. The mean rates of conversion were very high, however, in slices of skin obtained from several perineal sites (labia majora, scrotum, prepuce, and clitoris). Furthermore, as measured here, the rate of dihydrotestosterone formation by prepuce rises during the three months following birth and then falls progressively thereafter, reaching a level in the adult that is almost as low as that observed in the slices of non-perineal skin from all ages. In the patients with testicular feminization dihydrotestosterone formation by slices of skin obtained from the mons was within the normal range whereas the rates observed in labia majora were lower than the average values obtained in the normal subjects. In view of the fact that dihydrotestosterone is a potent androgen in man as well as in the rat, and in view of the fact that dihydrotestosterone rather than testosterone itself is a predominant form of the hormone bound to the nuclear chromatin of rat prostate, a presumed site of action of the hormone, the possibility must be considered that the ability to form this metabolite may be related in some way to the capacity of some tissues to develop an androgenic response to testosterone.