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: t o determine whether other steroids, such as dexamethasone (DEX), simil arly affect ST activity, and whether they alter St gene expression. Th e modulation of rat liver STs by the two steroidal compounds was exami ned at bath the enzyme activity and mRNA levels, PCN (75 mg/kg daily f or 4 days) increased liver phenol ST activity toward 1-naphthol and es trone, 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 an ST activities toward 1-nap hthol, estrone, and DHEA, but DEX markedly increased ST activity towar d dopamine and suppressed the N-OH-2AAF ST activity. Northern-blot ana lysis showed that PCN (75 mg/kg, single injection) had no effects an m RNA levels of phenol ST (ST1A1), N-OH-2AAF ST (ST1C1), and estrogen ST (ST1E2), but PCN significantly increased mRNA levels of hydroxysteroi d 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 suppre ss ST1C1, which corresponds to changes in encoded ST activity. Althoug h DEX increased ST activity toward DHEA, as did PCN, DEX had less effe ct on hydroxysteroid ST mRNA levels. These results suggest that STs ar e regulated by steroids, but DEX and PCN regulate the STs differently. The change in ST enzyme activity seems to be partially caused by alte ration in mRNA levels.