Delayed expression of neonatal sexual differentiation of corticosteroid patterns in rat bile.

The excretion of corticosterone metabolites in bile from male and female rats 21 to 56 days of age was studied. No sexual differences were observed in rats 21 and 28 days of age; in these animals 3β, 11β,21-trihydroxy-5α-pregnan-20-one disulfate was the major corticosteroid but significant amounts of monosulfurylated 3α,11β,21-trihydroxy-5α-pregnan-20-one and 3α,11β,15α,21-tetra-hydroxy-5α-pregnan-20-one were also excreted. From 35 days of age, sexual differences became successively more apparent in the biliary steroid excretion patterns and at 56 days of age female rats had developed a characteristic pattern of mono- and disulfurylated 3α,11β,15α,21-tetra-hydroxy-5α-pregnan-20-one whereas the male biliary steroid pattern was characterized by the complete absence of 15-hydroxylated corticosteroids, by relatively large amounts of 3β,11β,21-trihydroxy-5α-pregnan-20-one disulfate and by the sex-specific metabolite 5α-pregnane-3β,11β, 20β,21-tetrol disulfate. It is concluded that the “programming” or “imprinting” of hepatic corticosteroid metabolism that occurs in neonatal male rats and results in the absence of 15-hydroxy corticosterone metabolites and the presence of 5α-pregnane-3β, 11β,20β,21-tetrol in bile of adult male rats is not expressed until after puberty.