Androgen influences transforming growth factor-beta 1 gene expression in human adrenocortical cells

Sex steroid hormones have been shown to affect adrenocortical function and trophism, yet little is known about androgen action in human adrenocortical gland. In this study we examined the effects of androgens on transforming growth factor-beta 1 (TGF beta 1) production by the human adrenocortical ce ll line, NCI-H295, which we recently demonstrated to express androgen recep tor and whose growth is significantly reduced by dihydrotestosterone (DHT) treatment. TGF beta 1 is an important regulator of human adrenal development, with mar ked effects on steroid-producing cell function, and the production of disti nct TGF beta subtypes has been suggested to be regulated by steroid hormone s in several tissues. To address potential TGF beta 1 induction by DHT, qua ntitative PCR and enzyme-linked immunoadsorbent assay were performed in NCI -H295 cells treated with DHT (from 10(-12)-10(-9) mol/L). DHT led to a sign ificant dose-dependent increase in TGF beta 1 messenger ribonucleic acid ex pression and in biologically active TGF beta 1 protein levels in the condit ioned media of NCI-H295 cells, demonstrating that androgen can induce TGF b eta 1 expression and production. TGF beta 1 (10(-7)-10(-6) mol/L) was capab le of significantly reducing cell proliferation (P < 0.05) after 24 h of tr eatment, as assessed by measuring [H-3]thymidine incorporation in NCI-H295 cells. The addition of TGF beta 1-neutralizing antibody to cell cultures tr eated with different DHT concentrations (10(-9) and 10(-10) mol/L) blocked the inhibitory effect of TGF beta 1 on adrenocortical cell proliferation. These findings suggest that TGF beta 1 exerts an inhibitory action on adren ocortical cell proliferation. Therefore, it might be reasonable to suppose that DHT could also influence human adrenocortical cell growth by involving TGF beta 1.