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Summary. The metabolism of testosterone and 4-androstene-3,17-dione was studied in rat liver preparations after a single injection of carbon tetrachloride or phalloidin respectively and after oral administration of ethanol. The following results were obtained:After carbon tetrachloride and phalloidin the reduction rate of both steroids decreased rapidly (p < 0.001) in liver tissue sections as well as in microsomal preparations containing a NADP-regenerating system. It is therefore concluded, that this is a direct effect on the enzyme protein of the 4,5-dihydrosteroid:/qADPoxidoreductase.After ethanol the reduction capacity is also significantly (p < 0.001) depressed but it becomes normal if ethanol administration is stopped. Under special conditions with the NADP-regenerating system added to the microsomal preparation no depression of the reduction capacity is seen. In this case it is assumed that the depression of reduction rate is caused by a lack of coenzyme and is reversible.
Summary. The metabolism of testosterone and 4-androstene-3,17-dione was studied in rat liver preparations after a single injection of carbon tetrachloride or phalloidin respectively and after oral administration of ethanol. The following results were obtained:After carbon tetrachloride and phalloidin the reduction rate of both steroids decreased rapidly (p < 0.001) in liver tissue sections as well as in microsomal preparations containing a NADP-regenerating system. It is therefore concluded, that this is a direct effect on the enzyme protein of the 4,5-dihydrosteroid:/qADPoxidoreductase.After ethanol the reduction capacity is also significantly (p < 0.001) depressed but it becomes normal if ethanol administration is stopped. Under special conditions with the NADP-regenerating system added to the microsomal preparation no depression of the reduction capacity is seen. In this case it is assumed that the depression of reduction rate is caused by a lack of coenzyme and is reversible.
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 pC) in 250 ml Krebs-Ringer-bicarbonate solution. I n 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 5a-androstanediols than the liver of male rats. The quotient 5a-/5/?-dihydrotesterosterone in females has a value of 2.63 and that in male rats is equal to 0.68. The production of 5/?-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 5a-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 5cr-androstanediol is caused through an increase in the activity of 5a-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.I n den letzten Jahren ist mehrfach gezeigt worden, da13 die isoliert perfundierte Rattenleber zur Beantwortung vieler Stoffwechselprobleme erfolgreich herangezogen werden kann [l]. I m Vergleich mit den anderen in vitro-Systemen wie Homogenat und Schnittinkubation, besitzt die perfundierte Rattenleber neben den allgemeinen Vorteilen der
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