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Androgen Influences Transforming Growth Factor-ß1 Gene Expression in Human Adrenocortical Cells¹

Department of Biomedical Sciences and Advanced Therapies, Section of Endocrinology, University of Ferrara, 44100 Ferrara, Italy

Address all correspondence and requests for reprints to: Ettore C. degli Uberti, M.D., Department of Biomedical Sciences and Advanced Therapies, Section of Endocrinology, University of Ferrara, Via Savonarola 9, 44100 Ferrara, Italy. E-mail: ti8{at}dns.unife.it

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-ß1 (TGFß1) 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.

TGFß1 is an important regulator of human adrenal development, with marked effects on steroid-producing cell function, and the production of distinct TGFß subtypes has been suggested to be regulated by steroid hormones in several tissues. To address potential TGFß1 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 TGFß1 messenger ribonucleic acid expression and in biologically active TGFß1 protein levels in the conditioned media of NCI-H295 cells, demonstrating that androgen can induce TGFß1 expression and production. TGFß1 (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 [³H]thymidine incorporation in NCI-H295 cells. The addition of TGFß1-neutralizing antibody to cell cultures treated with different DHT concentrations (10^-9 and 10^-10 mol/L) blocked the inhibitory effect of TGFß1 on adrenocortical cell proliferation.

These findings suggest that TGFß1 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 TGFß1.

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