Retinoic acid inhibits hydrocortisone-stimulated expression of phenol sulfotransferase in bovine bronchial epithelial cells

The airway epithelium, which is commonly exposed to xenobiotics, contains the conjugative enzyme phenol sulfotransferase (PST). We have previously reported that hydrocortisone (HC) stimulates the expression of PST severalfold in cultured bovine bronchial epithelial cells (Beckmann et al., 1994, J. Cell. Physiol. 160:603 - 610). Here we report that this stimulation is attenuated by retinoic acid (RA). Dose-response measurements of both enzyme activities and mRNA levels indicated a 50% inhibition of HC-stimulated PST expression with 0.05 nM RA. Varied concentrations of RA had a general repressive effect on HC-stimulated PST expression, with no change in the half-maximal HC stimulatory concentration of 12.5 nM. Steady state kinetic measurements indicated no significant changes in apparent K-m values of 3-5 mu M for the acceptor substrate, 2-naphthol; only HC- and RA-dependent changes in V-max were observed. These changes were likely due to altered enzyme expression, as evidenced by immunoblot and Northern blot hybridization analyses. Thus, the expression of PST within bronchial epithelial cells is not merely constitutive, but is subject to both positive and negative controls. (C) 1996 Wiley-Liss, Inc.