Activin and inhibin have opposite effects on steroid 5 alpha-reductase activity in genital skin fibroblasts.
The transforming growth factor beta (TGF-beta) superfamily includes several closely related peptides including the activins and inhibins. Since we recently reported that TGF-beta 1 and beta 2 are potent inducers of steroid 5 alpha-reductase (5 alpha R), we have now studied the effects of these other peptides using primary cultures of human scrotal skin fibroblasts. Recombinant human activin A or inhibin A were added to cultured cells (2 x 10(5) cells) for 2 days in a serum free media and 5 alpha R activity was measured by the %-conversion of tracer [3H]-testosterone to dihydrotestosterone (DHT) over a 4-h period. Activin significantly stimulated 5 alpha R activity in a dose related manner (control 3.0 +/- 0.4%, activin (1.2 x 10(-9) M) 6 +/- 0.7%, P < 0.01, (2.4 x 10(-9) M) 8.5 +/- 0.6%, P < 0.001). In comparison, androgen (DHT 10(-7) M) induction of 5 alpha R was 4.7 +/- 0.2%, P < 0.05. Combined exposure of fibroblasts to activin (1.2 x 10(-9) M) and androgen (10(-7) M) did not result in additive or synergistic effect on 5 alpha R activity. In contrast, exposure of cells to an androgen (10(-7) M) and TGF-beta (2 x 10(-10) M) led to synergistic effects on 5 alpha R activity (control 1.5 +/- 0.1%, DHT 2.6 +/- 0.2% TGF-beta 1 4.8 +/- 0.5, TGF-beta 1 + DHT 9.2 +/- 1.2%).(ABSTRACT TRUNCATED AT 250 WORDS)
Antonipillai
I
I
University of Southern California, Division of Endocrinology, Los Angeles 90033, USA.
Wahe
M
M
Yamamoto
J
J
Horton
R
R
D015096:3-Hydroxysteroid Dehydrogenases / Q000032:analysis; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D028341:Activins; D013196:Dihydrotestosterone / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D018120:Finasteride / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D007265:Inhibins / Q000494:pharmacology*; D008297:Male; D011994:Recombinant Proteins / Q000494:pharmacology; D012611:Scrotum / Q000201:enzymology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D013196:Dihydrotestosterone; D028341:Activins; D007265:Inhibins; D018120:Finasteride; D015096:3-Hydroxysteroid Dehydrogenases; C063640:5alpha-androstane-3alpha-hydroxysteroid dehydrogenase; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase