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

The influence of the pancreatic hormones insulin and glucagon on the activity of tyrosine a-ketoglutarate transaminase and tryptophane oxydase in the rat liver has been investigated in vivo and in the isolated perfused rat liver. A direct action of both glucagon and insulin could be demonstrated. Insulin and glucagon led to an increased activity of tyrosine a-ketoglutarate transaminase in vivo as well as in the perfused liver. The maximum effect (insulin 2.6-fold; glucagon 1.8-fold) was found after 2 hours.I n the isolated perfused rat liver glucagon was found less effective than it was in vivo. To explain this difference a possible stimulation of insulin secretion by glucagon in wivo is being discussed.Both, insulin-and glucagon-effected increase of tyrosine a-ketoglutarate transaminase activity could be inhibited by actinomycin D and cycloheximide in vivo as well as in perfusion experiments.Further investigations on a possible d u e n c e of pancreatic hormones on tryptophane oxydase activity showed effects without statistical significance neither in vivo nor in the perfused liver. (Fig. 1).

This paper deals with investigations in isolated perfused rat livers on tryptophan-oxygenase activity under various experimental conditions. Enzyme-activity showed a linear rise with rising amounts of tryptophan (0; 125 and 250 mg of tryptophan/kg) in the perfusate. Adrenalectomized and sham-operated animals have been compared and activity in the adrenalectomized rats were significantly lower in all cases.A significant decrease in the substrate induc'ed increase of tryptophan-oxygenase-activity occured 12 h after adrenalectomy. Substrate-concentration was 250 mg/kg in these experiments.The influence of substrate and cortisol on tryptophan-oxygenase-activity has been investigated 7 days after operation. Combined application of both substrate and steroid resulted in no difference to sham-operated animals when compared to substrate only in the same concentration. On the other hand, in livers from adrenalectomized rats values were significantly higher with combined application than in livers of adrenalectomized animals which received substrate only.The substrate-dependent rise in tryptophan-oxygenase-activity could not be influenced by actinomycin D in contrast to the cortisol effect .which was significantly inhibited under these conditions. Both "inducers" were inhibited by cyoloheximid.These inhibition-experiments suggest and confirm two different mechanisms of the substrate-activation and steroid-induction of tryptop ban-oxygenase. (adrenal-ektomierte Tiere 0,9 Oi0 NaC1-Losung).Alle Operationen wurden in Evipan-NatriumNarkose durchgefuhrt ; die Dosierung betrug 0,2 ml/

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