Specific reductive metabolism of steroid sulphates in rat liver

The reductive metabolism of steroid sulphates and corresponding unconjugated steroids has been investigated in male and female rat liver. Enzyme activities studied were 5alpha-reductase, 5beta-reductase and 3alpha-, 3beta- and 20beta-hydroxy-steroid oxidoreductases in microsomal and soluble cellular fractions. With the exception of microsomal 3alpha-reductase all enzymes were equally or more active using sulphoconjugated substrates than using corresponding unconjugated substrates. 20beta-reduction of corticosterone and deoxycorticosterone occurred only with the 21-sulphurylated derivatives. This sulphate-specific 20beta-reductase, which is only present in male rat liver, probably participates in the formation of the sex-specific 20beta-reduced corticosterone metabolites present in bile from male but not from female rats. Sulphoconjugated deoxycorticosterone and corticosterone were also better substrates for microsomal 5alpha-reductase and sulphoconjugated 5alpha-dihydrotestosterone for microsomal 3beta-hydroxysteroid oxidoreductase than the corresponding unconjugated analogues. In conclusion, these results indicate that steroid sulphates generally are good substrates for hepatic reducing enzymes; in many cases even better substrates than the unconjugated analogues.