Abstract
Transforming growth factor-β (TGF-β) was found to inhibit basal and ACTH-stimulated steroid production by cultured human fetal adrenal cells. The inhibitory effects of TGF-β 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 ≥ 0.1 ng TGF-β/ml. The inhibitory effects of l ng/ml TGF-β on ACTH-stimulated DS production were more striking than those on cortisol production by both fetal zone and neocortical cells. TGF-β also was found to interfere with DS and cortisol production by fetal zone cells in response to forskolin and dibutyryl cAMP. TGF-β interfered with ACTH stimulation of cytochrome P450 17α mRNA in fetal zone and neocortex cells. These results are suggestive that TGF-β differentially inhibits DS and cortisol production by human fetal adrenal cells and that the site of TGF-β action on steroidogenesis may be distal to the generation of cAMP. Such results, along with those of others, are suggestive that TGF-β may play an autocrine/paracrine role in the human adrenal.
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