肝のクエン酸生成に関する研究:第二報 実驗的肝障害時の肝クエン酸生成に及ぼすEstrogenの影響について
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By the administration of sodium monofluoroacetate (S F A) it was found that the livers of female rats accumulated large quantities of citric acid as in the case of other organs whereas male rats did not. Such sex difference in citrate synthesis was presumed to be due to the influence of sex hormones. The present investigation was undertaken to attempt to elucidate whether such sex difference is observed or not even in the liver citrate synthesis when liver injury was experimentally induced by carbon tetrachloride (CCl<SUB>4</SUB>), which attack liver mitochondria and disorganised the enzyme system' with special reference to estrogen treatment. The following results were thus obtained.<BR>1. No significant difference was observed in the amount of liver citrate in S F A-treated male rat after liver injury with CCl<SUB>4</SUB> for comparison with normal male rat treated with SFA. However a decrease in citrate synthesis was observed in the female rat with damaged liver as compared with normal female rat. Further, citrate synthesis in kidney of rats in both sexes was markedly decreased after treatment of CCl<SUB>4</SUB>.<BR>2. The livers of female rat treated with CCl<SUB>4</SUB> accumulated the large quantities of citric acid following S F A administration in comparison to similarly treated male rats. This fact would indicate that sex difference in citrate synthesis in liver remain unchanged despite the liver is affected considerably with CCl<SUB>4</SUB>. Contrary to this, no sex difference was noticed in the kidney citrate after treatment with CCl<SUB>4</SUB>. In this case, histological changes in the liver of females were severe than in that of the males.<BR>3. Increased amounts of CCl<SUB>4</SUB> was administered to only female rat, no significant difference in accumulation of both of the liver and kidney citrate was observed following S F A treatment compared with female rat injected not increased amounts of CCl<SUB>4</SUB>. However, in microscopically, higher degenerative changes in every liver cell were noticed in the group of animals received increased amount of CCl<SUB>4</SUB>.<BR>4. When such a high dose of estradiol benzoate as 2mg/kg was administered for 6 deys simultaneously with CCl<SUB>4</SUB> and sacrificed after treatment of S F A, no significant difference or even a tendency of decrease was noted in the amounts of liver and kidney citrates compared with those of the group of animals received CCl<SUB>4</SUB> alone. Moreover, the highest degree of damage in the liver cells was recognized in histological picture after trea-tment of estrogen plus CCl<SUB>4</SUB>.<BR>5. As it was presumed that estrogen inhibits citrate synthesis in liver, the author administered a high dose of estradiole benzoate to the normal female rats for the same period of time and observed a marked inhibition in the accumulation of liver citrate following treatment of SFA. Nevertheless, the level was found much higher than that of the group of animals which received CCl<SUB>4</SUB> plus estrogen, Furthermore, microscopically no pathological changes were observed in the female rat liver administered with estrogen.<BR>6. When a decreased dose of estrogen (1/10 of the dose of estradiol benzoate in the preceding experiment-0.2mg/kg) was similarly administered and then treated with S F A, the slight accumulation of liver citrate was noticed but the value was found still lower compared with the normal female rat.<BR>7. Administration of 0.2mg/kg of estradiol benzoate for 6 days to pregnant rats followed SFA treatment caused a marked increase in the citrate content of liver.
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