Specific metabolic pathways of steroid sulfates in human liver microsomes

The hydroxylation of steroid sulfates has been studied in liver microsomal preparations from adult humans. Ten different C18, C19, and C21 steroid sulfates and the corresponding unconjugated steroids were used as substrates. In several cases it was found that steroid sulfates were efficiently hydroxylated in a way that differed both qualitatively and quantitatively from the hydroxylation of the corresponding unconjugated substrates. Only the hydrophobic (nonsulfurylated) end of the steroid sulfate molecule was hydroxylated. The steroids sulfurylated in position 3 were generally better substrates for the liver microsomal hydroxylase system than those sulfurylated in position 17. The findings that unconjugated and sulfoconjugated steroids are metabolized along different pathways in the liver may be of general significance. Sulfoconjugation and subsequent hydroxylation may also be an important pathway in the metabolism of xenobiotics in man.