Metabolism of Corticosterone in the Isolated Perfused Rat Liver

[4‐¹⁴C]Corticosterone was perfused through isolated livers from male and female rats. Bile, perfusate and liver tissue were extracted and analysed separately. No specific differences were observed in the distribution of various isomers of corticosterone metabolites isolated from these three sources. However, the radioactive metabolites with the chromatographic property of steroid glucuronides were mainly present in the bile. Male rat livers metabolized corticosterone into the following 20‐hydroxy compounds: 5α‐pregnane‐3α, 11β, 20β(and 20α), 21‐tetrol and 5α‐pregnane‐3β, 11β, 20β,21‐tetrol. In female rat livers, on the other hand, only small amounts of 5α‐pregnane‐3β,11β,20β,21‐tetrol were formed. The predominant corticosterone metabolites isolated after perfusion of female rat livers were identified as 3α(and 3β), 11β,15α,21‐tetrahydroxy‐5α‐pregnan‐20‐one and 3α(and 3β),11β,21‐trihydroxy‐5α‐pregnan‐20‐one. Furthermore, female rat livers produced a larger amount of mono‐and disulphurylated metabolites than male livers. All these findings agree well with what has previously been found concerning the excretion of steroids in faeces from germfree rats. The present results therefore show that an important reason for the large sexual differences observed in rats in the faecal and urinary steroid patterns is a different hepatic metabolism of steroids in male and female rats.