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)
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Dept. of Medicine, University of Southern California School of Medicine, Los Angeles 90033.
Antonipillai
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Horton
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D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000096:biosynthesis*; D000818:Animals; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D013196:Dihydrotestosterone / Q000378:metabolism / Q000494:pharmacology; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012611:Scrotum / Q000166:cytology / Q000201:enzymology*; D013739:Testosterone / Q000378:metabolism / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D016895:Culture Media, Serum-Free; D016212:Transforming Growth Factor beta; D013196:Dihydrotestosterone; D013739:Testosterone; D004815:Epidermal Growth Factor; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase