Sex-dependent regulation by dexamethasone of murine hydroxysteroid sulfotransferase gene expression

Toxicol Lett. 2001 Mar 8;119(3):235-46. doi: 10.1016/s0378-4274(01)00263-6.

Abstract

To determine whether glucocorticoid-inducible expression of hepatic hydroxysteroid sulfotransferase is conserved in mouse, the effects of dexamethasone (DEX) on hydroxysteroid sulfotransferase (mSULT2A) gene expression were investigated in primary cultured hepatocytes prepared from C57BL/6J mice. In female mouse hepatocytes, DEX (10(-7) and 10(-5) M, respectively) produced 8.2- and 17.8-fold increases, respectively, in the amounts of mSULT2A mRNA relative to control. By contrast, mSULT2A mRNA levels were undetectable in male mouse hepatocytes. Female-predominant mSULT2A mRNA expression was also observed in liver samples from C57BL/6J and three other mouse strains. Treatment of primary cultured female mouse hepatocytes with dihydrotestosterone in the presence of DEX suppressed mSULT2 expression. Transfection of primary cultured male or female mouse hepatocytes with a rat SULT2-40/41 reporter construct revealed that hepatocytes of both sexes have sufficient machinery to achieve DEX-inducible SULT2 transcription. However, treatment with the potent histone deacetylase inhibitor trichostatin A failed to elicit mSULT2A expression in male mouse hepatocytes.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Autoradiography
  • Cells, Cultured
  • DNA, Complementary
  • Dexamethasone / pharmacology*
  • Female
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Liver / drug effects*
  • Liver / enzymology
  • Luciferases / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Sex Characteristics
  • Species Specificity
  • Sulfotransferases / genetics
  • Sulfotransferases / metabolism*
  • Transfection

Substances

  • Anti-Inflammatory Agents
  • DNA, Complementary
  • Dexamethasone
  • Luciferases
  • Sulfotransferases
  • alcohol sulfotransferase