Effects of transforming growth factor beta and epidermal growth factor on steroid 5 alpha-reductase activity in genital skin fibroblasts.

Regulation of steroid 5 alpha-reductase (5 alpha R) activity and dihydrotestosterone (DHT) formation is central to prostate and sexual skin (hair) growth and cell function. Transforming growth factor-beta 1 (TGF-beta 1) is a ubiquitous peptide present in skin and scrotal tissue and its receptor is universally expressed. We have explored the role of TGF-beta 1 and -beta 2 on androgen formation in skin. Rat or human sexual skin fibroblasts were grown in primary cultures (passage 3-7). 5 alpha-Reductase activity was measured by the %-conversion of tracer 3H-testosterone to dihydrotestosterone over a 4 h period. Incubation of scrotal fibroblasts (2 x 10(5) cells) in serum and growth factor free media with androgen, such as DHT for two days significantly stimulates 5 alpha R in these cells (1.6-fold, p < 0.05 vs control). TGF-beta 1 alone at picomolar concentrations (2 x 10(-11) M to 2 x 10(-10) M) was a potent inducer of 5 alpha R activity in both rat (1.8-fold and 2.8-fold, respectively, p < 0.001 vs control at both doses) and human cells (TGF-beta 1 2 x 10(-10) M 3.3-fold, p < 0.001 vs control). Combined exposure of these fibroblasts to TGF-beta 1 (2 x 10(-10) M) and androgen (10(-7) M) further potentiated 5 alpha R activity (rat cells 6.5-fold, human cells 6.4-fold, p < 0.001 vs DHT or TGF-beta 1 alone).(ABSTRACT TRUNCATED AT 250 WORDS)