Effects of transforming growth factor-beta on human fetal adrenal steroid production

Transforming growth factor-beta (TGF-beta) was found to inhibit basal and ACTH-stimulated steroid production by cultured human fetal adrenal cells. The inhibitory effects of TGF-beta were both time and dose-dependent. Inhibition of basal dehydroepiandrosterone sulfate (DS) production usually was noted only after 3 or more days of treatment with > or = 0.1 ng TGF-beta/ml. The inhibitory effects of 1 ng/ml TGF-beta on ACTH-stimulated DS production were more striking than those on cortisol production by both fetal zone and neocortical cells. TGF-beta also was found to interfere with DS and cortisol production by fetal zone cells in response to forskolin and dibutyryl cAMP. TGF-beta interfered with ACTH stimulation of cytochrome P450(17) alpha mRNA in fetal zone and neocortex cells. These results are suggestive that TGF-beta differentially inhibits DS and cortisol production by human fetal adrenal cells and that the site of TGF-beta action on steroidogenesis may be distal to the generation of cAMP. Such results, along with those of others, are suggestive that TGF-beta may play an autocrine/paracrine role in the human adrenal.