Effects of ACTH and cytokines on dehydroepiandrosterone sulfotransferase messenger RNA in human adrenal cells

Dehydroepiandrosterone sulfate (DS) is the major adrenal androgen produced in the fetal and adult human; its formation is dependent upon the action of dehydroepiandrosterone sulfotransferase (DST). Since the factors that regu late DST are poorly characterized, we investigated the effects of ACTH, whi ch stimulates DS production, and the cytokines transforming growth factor-b eta (TGF-beta), and tumor necrosis factor-a (TNF-alpha), both of which are inhibitory to adrenal steroidogenesis, on cultured human fetal adrenal cell s. Cellular levels of DST mRNA were increased in a dose dependent fashion i n response to ACTH; DST mRNA was less responsive to ACTH stimulation than w as 17 hydroxylase (CYP 17) mRNA. The stimulatory effects of ACTH on DST mRN A levels were blunted by both TGF-beta and TNF-alpha; the inhibitory effect s of TNF-alpha on DST mRNA were more striking than were those on CYP 17 mRN A. These data suggest that DS production can be altered by several agents a cting on the DST gene.