Abnormal Metabolism of Steroid Hormone in the Liver of Tumor-Bearing Rats:Changes in Δ4-Hydrogenase Activity

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Δ4-Hydrogenase is one of the most crucial enzymes in steroid hormone metabolism. The present study was designed to investigate if any change in Δ4-hydrogenase activity is detected in the liver of tumor-bearing rats. Through all experiments, Δ4-hydrogenase activity was determined by Tomkins' method, by measuring the rate of decrease in optical density of three steroid substrates: compounds E, B, and F. Minced rhodamine sarcoma was implanted subcutaneously on the backs of male Wistar rats. After the implantation, the rats were decapitated at weekly intervals for the periods up to six weeks, and the Δ4-hydrogenase activity of the liver was measured. After the six weeks, all the implanted sarcomas were extirpated, and the Δ4-hydrogenase activity of the survived rats was further followed for two weeks. The results of the experiments were given in Fig. 2 and TABLE I. Each point represents an average of the values obtained from five rats. The Δ4-hydrogenase activity increased in the course of the first week after the implantation, returned almost to normal in the course of the second to third weeks and decreased remarkably in the course of the fourth to sixth weeks. This decrease in the activity, however, rapidly returned to normal in two weeks after extirpation of the sarcomas. The mechanism of the initial increase of the Δ4-hydrogenase activity is hard to be clarified yet with the present experiment, but it may be possible that the implanted tumor might enhance ACTH secretion, which results in an increased production of steroid hormone and then in a high activity of this enzyme. The decrease in the enzyme activity in the late stage of tumor-growth also is hard to be explained. The decrease in the activity of this enzyme in fasting animals is already noticed by several authors. In the present experiment, the tumor-bearing rats were fasted for 24 hours at the sixth week after tumor implantation. As shown in Fig. 3, further decrease in the Δ4-hydrogenase activity was observed in the tumorbearing rats which were fasted for 24 hours. Secondly, 200 micrograms of cortisol or triamcinolone were injected intraperitoneally into each normal rat after 24 hours of fasting. In four hours, the Δ4-hydrogenase activity in the liver was measured. The results, as shown in Fig. 4, revealed that steroid hormone substrate enhanced the activity of Δ4-hydrogenase. All the above results were affirmed further by administering 200 micrograms of triamcinolone to each of five rhodamine sarcoma-bearing rats (five weeks after implantation) and five fasting normal rats. The liver homogenate was separated into soluble and microsome fraction in this experiment. The results are illustrated in Fig. 5. Again Δ4-hydrogenase activity of the liver of the fasting normal animals and the tumor-bearing animals were depressed, and their enzyme activities were increased remarkably after administration of triamcinolone. The degree of increase in the enzyme activity in the tumor bearing-rats was, however, lower than that in the normal fasting animals. The responses to hormone injection of Δ4-hydrogenase activity was more remarkable in the soluble fraction than in the microsome fraction. The increase of the activity of Δ4-hydrogenase might be explained as a result of substrate induction or of suppressed break down of the enzyme by the substrate.

Abnormal Metabolism of Steroid Hormone in the Liver of Tumor-Bearing Rats:Changes in Δ<SUP>4</SUP>-Hydrogenase Activity

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