Regulation of hepatic sulfotransferases by steroidal chemicals in rats.
Pregnenolone-16 alpha-carbonitrile (PCN) has previously been shown to increase sulfotransferase (ST) activity in rats. It was of interest to determine whether other steroids, such as dexamethasone (DEX), similarly affect ST activity, and whether they alter ST gene expression. The modulation of rat liver STs by the two steroidal compounds was examined at both the enzyme activity and mRNA levels. PCN (75 mg/kg daily for 4 days) increased liver phenol ST activity toward 1-naphthol and estrone, and hydroxysteroid ST activities toward dehydroepiandrosterone (DHEA) and bile acids; but, PCN had no effects on ST activities toward dopamine and N-hydroxy-2-acetylaminofluorene (N-OH-2AAF). DEX (50 mg/kg daily for 4 days) had similar effects on ST activities toward 1-naphthol, estrone, and DHEA, but DEX markedly increased ST activity toward dopamine and suppressed the N-OH-2AAF ST activity. Northern-blot analysis showed that PCN (75 mg/kg, single injection) had no effects on mRNA levels of phenol ST (ST1A1), N-OH-2AAF ST (ST1C1), and estrogen ST (ST1E2), but PCN significantly increased mRNA levels of hydroxysteroid ST (ST-20/21, ST-40/41, and ST-60). DEX (50 mg/kg, single injection), in contrast, increased the mRNA levels of ST1A1 and tended to suppress ST1C1, which corresponds to changes in encoded ST activity. Although DEX increased ST activity toward DHEA, as did PCN, DEX had less effect on hydroxysteroid ST mRNA levels. These results suggest that STs are regulated by steroids, but DEX and PCN regulate the STs differently. The change in ST enzyme activity seems to be partially caused by alteration in mRNA levels.
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Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City 66160-7417, USA.
Klaassen
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D000818:Animals; D003687:Dehydroepiandrosterone / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004789:Enzyme Activation; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D011285:Pregnenolone Carbonitrile / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013256:Steroids / Q000494:pharmacology*; D015238:Sulfotransferases / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D013256:Steroids; D011285:Pregnenolone Carbonitrile; D003687:Dehydroepiandrosterone; D003907:Dexamethasone; D015238:Sulfotransferases