Testosterone metabolism in the isolated perfused rat liver

Abstract

The metabolism of testosterone was studied in perfused livers of normal male and female rats and of male rats, four days and four weeks after castration. The rats were treated twenty days with cyproterone acetate and cyproterone and four days with phenobarbital (Luminal). Livers were perfused with [4‐14C]testosterone (7.2 mg, 9 μC) in 250 ml Krebs‐Ringer‐bicarbonate solution. In some experiments the metabolism of testosterone was measured under perfusion conditions without oxygen and with addition of albumin in the perfusion medium.The isolated perfused rat liver shows a sex difference in the metabolism of testerone. The liver of females produces more 5α‐androstanediols than the liver of male rats. The quotient 5α‐/5β‐dihydrotesterosterone in females has a value of 2.63 and that in male rats is equal to 0.68. The production of 5β‐dihydrotestosterone is significantly smaller in female than in male rats. The quotient of the highly polar (H) and remaining metabolites (R) in male animals is 1.2 and that in female rats is only 0.5. The small quotient in the female rats is explained by the significant elevation of the remaining metabolites through the more active 5α‐reductase.Four days after castration of male rats, we can see a very significant decrease of the hydroxymetabolites (H) and a significant increase of the remaining metabolites (R). So we find a quotient H/R of 0.33 in the males as compared to that in the females (0.5). The elevation of the remaining metabolites, based on a significant increase in the production of 5α‐androstanediol is caused through an increase in the activity of 5α‐reductase after castration.We could observe a similar change in the metabolism in rat liver after four weeks castration, but the differences are not so marked as in four day castrated animals.After a twenty day application of cyproterone acetate, the metabolism of testosterone showed no important changes, except the absence of androstenedione. Application of cyproterone indicated a significant increase of the hydroxymetabolites. The reason for this will probably be found in an induction of the microsomal oxydases.After a four day treatment with phenobarbital (Luminal) the hydroxymetabolites show a significant increase, which can be explained by an induction of the microsomal oxydases.Under conditions without oxygen, the metabolism of testosterone significantly declines. As expected we find less highly polar derivatives.On addition of albumin to the perfusion medium, we observe a significant three fold increase in the metabolism of testosterone.