The formation of 16,17-dihydroxylated C₁₉ steroids from 10-dehydro C₁₉ steroids in liver microsomes from male and female rats

The metabolism of the following substrates in liver microsomes from male and female rats was studied: 4,16-[7α-³H]androstadien-3-one, 5,16-androstadien-3β-ol, 5α-[7α-³H]androst-16-en-3α-ol, 5α-androst-16-en-3β-ol, 16α,17α-epoxy-5α-androstan3α-ol, 16α,17α-epoxy-5α-androstan-3β-ol and 3β-hydroxy-5,16-pregnadien-20-one. Liver microsomes from male rats were considerably more efficient in converting the 16-dehydro-C₁₉-steroids than were liver microsomes from female rats. Male liver microsomes metabolized 4,16-androstadien-3-one, 5α-androst-16-en-3α-ol and 5α-androst-16-en-3β-ol into isomers of 5α-androstane-3,16β,17α-triol and 3,17β-dihydroxy-5α-androstan-16-one whereas female liver microsomes formed isomers of both 5α-androstane-3, 16α,17β-triol and 5α-androstane-3,16β,17α-triol from the same substrates. 5,16-Androstadien-3β-ol was metabolized into 5-androstene-3β,16β,17α-triol by liver microsomes from male rats ; liver microsomes from female rats did not form any 16,17-dioxygenated steroids from this substrate. No 16,17-dioxygenated metabolites were formed from 3β-hydroxy-5,16-pregnadien-2o-one, neither with microsomes from male rats, nor with microsomes from female rats. When 16α,17α-epoxy steroids were used as substrates both male and female liver microsomes formed 16β,17α-dihydroxylated metabolites. The large sexual differences characterizing the metabolism of 16-dehydro C₁₉ steroids in liver microsomes from rats make the conversions described suitable assay systems for studying factors that regulate sexual differences in microsomal oxygenation reactions.