Variation in steroid 5 alpha-reductase activity in cloned human skin fibroblasts. Shift in phenotypic expression from high to low activity upon subcloning

Steroid 5 alpha-reductase in skin fibroblasts varies in two ways: 1) mean activity in uncloned fibroblasts corresponds to the activity in skin from which fibroblasts are derived (high in genital skin and low in nongenital skin); 2) activity in normal genital skin fibroblasts varies over a wide range (more than 200-fold). Studies of activity in fibroblast clones provides an explanation for this variability. Activity in clones of genital skin fibroblasts varies from the limits of detectability to very high levels, whereas activity in fibroblasts cloned from nongenital skin is uniformly low. The mean value of 5 alpha-reductase in genital skin clones is similar to the value in uncloned fibroblasts from the same explant. This suggests that the numbers of high and low activity cells in a given explant influence the overall enzyme activity. Variability among normal genital skin strains is also due to inherent differences in the range of enzyme activities. Furthermore, high activity genital skin clones give rise to a mixture of both high and low-activity subclones, whereas low activity genital skin and nongenital skin clones give rise to populations with uniformly low activity. Thus, with time genital skin gives rise to high activity fibroblasts that continually undergo shift in phenotypic expression to low activity.