EFFECTS OF MOLYBDATE AND PENTACHLOROPHENOL ON THE SULFATION OF DEHYDROEPIANDROSTERONE

Pentachlorophenol (PCP) and molybdate have been shown to inhibit the s ulfoconjugation of various chemicals in rats and therefore are useful to examine the role of sulfoconjugation on the toxicity of a chemical, PCP inhibits sulfation by competing with substrates for phenol-sulfot ransferases, but not hydroxysteroid-sulfotransferases. In contrast, mo lybdate decreases sulfation by limiting sulfate availability and there by decreasing the synthesis of 3'-phosphoadenosine 5'-phosphosulfate ( PAPS), which is the obligate cosubstrate for sulfation. Therefore, it was of interest to determine whether PCP or molybdate is effective in decreasing the in vivo sulfation of dehydroepiandrosterone (DHEA), whi ch is a substrate for hydroxysteroid-sulfotransferases. PCP (40 mu mol /kg ip) or molybdate (7.5 mmol/kg po) was given 45 min and 4 h, respec tively, prior to the start of DHEA infusion. The effects of these two sulfation inhibitors on DHEA sulfation were dependent on the rate of D HEA infusion in rats. PCP had different effects on the sulfation of va rious infusion rates of DHEA in rats. PCP had little effect on the sul fation after the two lowest infusion rates of DHEA (12.5 and 25 mg/kg) and actually increased (233%) DHEA-sulfate serum concentrations with the highest DHEA infusion rate (50 mg/kg). Although molybdate had litt le affect on the sulfation of the lowest DHEA infusion rate, it signif icantly decreased (50-85%) DHEA-sulfate serum concentrations with the two higher DHEA infusion rates. These data indicate that molybdate, un like PCP, decreases the sulfation of DHEA and may be a useful tool to decrease the sulfation of other substrates of hydroxysteroid-sulfotran sferases. (C) 1998 Academic Press.