Hepatic Bile Salt Sulfotransferases in the Rat

Abstract

SummaryBile salt sulfotransferase (BSS) activity for the fetal bile acid, 3β‐hydroxy‐5‐cholenoate, was first detected in the fetus at 18–19 days of gestation and was twofold greater than for glycolithocholate. The near‐term (20–21 days of gestation) and newborn pup BSS activity was only 5–10% of that in maternal liver. The 3β‐hy‐droxy‐5‐cholenoate sulfotransferase activity rose by the second day of life to levels observed in the mature male, and to activities greater than the mature female by the time of weaning at 3 weeks of age. Sex differences in 3β‐hydroxy‐5‐cholenoate sulfotransferase activity developed during adolescence (28–35 days of age), resulting in fivefold greater activity in the mature female compared with the male. Two isoenzyme activities (BSS I and BSS II) were identified in both sexes during development by DEAE‐Sephadex A‐50 ion‐exchange chromatography of liver cytosol. In the fetal and newborn liver, only one isoenzyme activity was distinctly identified for both monohydroxy bile acids, corresponding to BSS I in older rats. After the first week of life, both BSS I and BSS II exhibited activity like glycolithocholate, but only one peak of activity was identified for 3β‐hydroxy‐5‐cholenoate, corresponding to BSS I. The 3β‐hydroxy‐5‐cholenoate sulfotransferase activity in the mature male was only 20% of the mature female because of a decline in BSS I activity in the male during adolescence. BSS I and II were further purified by taurocholate‐Sepharose 4B chromatography. BSS I had a low affinity toward taurocholate passing through the column, whereas BSS II was absorbed and could be eluted from the column with 0.2 M NaCl. BSS I had four times the activity for 3β‐hydroxy‐5‐cholenoate vs. glycolithocholate, whereas the relative activity of BSS II for 3β‐hydroxy‐5‐cholenoate was only 6% of that for glycolithocholate. BSS I was completely inhibited by 0.1 m M 3‐ketolithocholate, whereas BSS II activity was inhibited only 13%. BSS I activity was enhanced by Co2+ and Zn2+, whereas BSS II activity was inhibited by these divalent ions. We concluded that the monohydroxy bile acids were sulfated by two distinct isoenzymes that could be separated by taurocholate‐Sepharose 4B chromatography. 3β‐Hydroxy‐5‐choleno‐ate was sulfated by BSS I, an isoenzyme regulated by gonadal hormones, which appeared to explain the marked sex differences in 3β‐hydroxy‐5‐cholenoate sulfotransferase activities in mature rats.