Hepatic 15‐Hydroxylation of Corticosteroids in the Rat

摘要: The substrate specificity of a sex-specific hepatic 15-hydroxylase active on different C21O2 and C21O3 steroids was studied in the isolated perfused liver from female rats. Liquid-chromatographic separation methods combination with computerized gas chromatography-mass spectrometry employed to identify metabolites formed. The majority (between 75 – 90%) 15-hydroxylated compounds were present as monosulphate conjugates while smaller amounts disulphates also detected. Hydroxylation found take place exclusively at position 15β. A certain number 11-deoxy-21 -hydroxy, 11-oxo-21-hydroxy 11,21-dihydroxy 3-keto-Δ4-, 3-keto-5α(5β)-, 3α,5α- or 3β,5β-structure readily converted 15β-hydroxy-lated metabolites. Depending structure substrate, between 20 87% total formed 15β-hydroxylated. 5α-Reduced better substrates for hydroxylase than corresponding 3-keto-Δ4- 5β-reduced compounds. configuration hydroxylgroup C-3 did not affect degree 15-hydroxylation. 11β-Hydroxylated served 11-dehydro-, 11-deoxy- 11 α-hydroxy 5α-Dihydrocorticosterone 3α,5α-tetrahydrocorticosterone best 15β-hydroxylase.