Androgen influences transforming growth factor-β1 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 cell line, NCI-H295, which we recently demonstrated to express androgen receptor and whose growth is significantly reduced by dihydrotestosterone (DHT) treatment. TGF beta 1 is an important regulator of human adrenal development, with marked effects on steroid-producing cell function, and the production of distinct TGF beta subtypes has been suggested to be regulated by steroid hormones in several tissues. To address potential TGF beta 1 induction by DHT, quantitative 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 significant dose-dependent increase in TGF beta 1 messenger ribonucleic acid expression and in biologically active TGF beta 1 protein levels in the conditioned media of NCI-H295 cells, demonstrating that androgen can induce TGF beta 1 expression and production. TGF beta 1 (10(-7)-10(-6) mol/L) was capable of significantly reducing cell proliferation (P < 0.05) after 24 h of treatment, as assessed by measuring [H-3]thymidine incorporation in NCI-H295 cells. The addition of TGF beta 1-neutralizing antibody to cell cultures treated 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 adrenocortical cell proliferation. Therefore, it might be reasonable to suppose that DHT could also influence human adrenocortical cell growth by involving TGF beta 1.