Metabolism of Androstenedione and Progesterone in the Isolated Perfused Rat Liver

[4‐¹⁴C]Androstenedione and [4‐¹⁴C]progesterone were perfused through isolated livers from male and female rats. The metabolites in bile, perfusate and liver tissue were identified by gas chromatography‐mass spectrometry. Livers from male rats metabolized androstenedione and progesterone predominantly to 2‐hydroxylated and 16‐hydroxylated compounds, i.e. isomers of 3,16‐dihydroxyandrostan‐17‐one, androstane‐3,16,17‐triol, androstane‐2,3,16,17‐tetrol, 2,3‐dihydroxypregnan‐20‐one, 3,16‐dihydroxypregnan‐20‐one, pregnane‐2,3,20‐triol and 2,3,16‐trihydroxypregnan‐20‐one. Most of these metabolites were found in the glucuronide fraction. Livers from female rats metabolized androstenedione mainly to 7‐hydroxylated and 15‐hydroxylated compounds, i.e. isomers of 3,7‐dihydroxyandrostan‐17‐one, androstane‐3,7,17‐triol and androstane‐3,15,17‐triol. These compounds were mainly present in the glucuronide fraction. Progesterone was predominantly metabolized into sulphates and “glucuronides” of 3α,15α‐, 3α,15β‐, and 3α,16α‐dihydroxy‐5α‐pregnan‐20‐one. When increasing amounts of progesterone were perfused through livers from female rats less sulphates and more “glucuronides” were formed. The results are discussed in relation to previous results regarding the sexual differences in the excretion of steroids in urine, faeces and bile from rats.