TESTOSTERONE INHIBITION OF 6BETA-, 7ALPHA- AND 16ALPHA- HYDROXYTESTOSTERONE METABOLISM BY RAT LIVER MICROSOMES

Testosterone-4-14C (900 mμmoles) is metabolized to 6β-, 7 α- and 16α-hydroxytestosterone in vitro by liver microsomes from adult male rats, but not to compounds more polar than these three products. The formation of 6β-, 7α- and 16α-hydroxytestosterone increases linearly with tissue concentration and incubation time. However, in the absence of testosterone, 6β-, 7α- and 16α-hydroxytestosterone-4-14C are metabolized by enzymes in liver microsomes to more polar compounds that absorb ultra-violet light. This metabolism of 6β-, 7α- and 16α-hydroxytestosterone to polar compounds is inhibited by the addition of testosterone to the incubation medium. The profile of testosterone metabolites formed by liver microsomes depends on the concentration of testosterone in the incubation mixture. When a high concentration of testosterone -4-14C is used as the substrate, less of the 6β-, 7α- and 16α-hydroxytestosterone formed is further metabolized to highly polar substances than when a low concentration of testosterone-4-14C is used as the substrate. This inhibition of the metabolism of 6β-, 7α- and 16α-hydroxytestosterone by testosterone is shown to be competitive. © 1969.