EFFECTS OF PORTAL-VEIN LIGATION ON SEX-HORMONE METABOLISM IN MALE-RATS - RELATIONSHIP TO LOWERED HEPATIC CYTOCHROME-P450 LEVELS
EFFECTS OF PORTAL-VEIN LIGATION ON SEX-HORMONE METABOLISM IN MALE-RATS - RELATIONSHIP TO LOWERED HEPATIC CYTOCHROME-P450 LEVELS
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DOI：
10.1016/0016-5085(86)90924-8
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发表时间：
1986-02-01
期刊：
影响因子：
29.4
通讯作者：
MURRAY, M
中科院分区：
文献类型：
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作者：
FARRELL, GC;KOLTAI, A;MURRAY, M
雄性大鼠的肝脏细胞色素P450水平在门静脉结扎后下降，门静脉结扎是一种产生门静脉血液全肝转流的过程。本研究旨在检验性激素代谢的变化是否可以解释这些降低的细胞色素P450水平。门静脉结扎导致睾丸萎缩和血清睾酮浓度降低。血清黄体生成素水平也降低，这表明睾丸萎缩是下丘脑-垂体-性腺轴抑制的继发因素。门静脉结扎后血清雌酮和雌二醇浓度显著升高，而尿总雌激素排泄量的增加幅度和延迟出现表明这主要是由于雌激素产生的增加。在雄性大鼠中，去势(12wk)和外源性雌激素注射均导致肝细胞色素P450水平和乙基吗啡N-脱甲基酶活性的变化，与门静脉结扎后的变化基本相似。然而，在雌性和去势雄性大鼠中，细胞色素P450不受门静脉结扎的影响。补充睾酮可纠正去势雄性大鼠细胞色素P450水平的变化，但对门静脉结扎雄性大鼠无此影响。结论：门静脉结扎后性激素代谢发生改变，可能与细胞色素P450和药物代谢酶活性改变有关。然而，在这个模型中，血清睾酮水平的降低并不能单独解释肝脏药物代谢的变化，而且抑制下丘脑-垂体因子似乎是重要的。
Hepatic cytochrome P450 levels in male rats fall after portal vein ligation, a procedure that produces total hepatic bypass of portal blood. The present study was undertaken to examine whether changes in sex hormone metabolism could account for these lowered cytochrome P450 levels. Portal vein ligation resulted in testicular atrophy and low serum testosterone concentrations. Serum luteinizing hormone levels were also reduced, suggesting that testicular atrophy was secondary to suppression of the hypothalamic-pituitary-gonadal axis. Serum estrone and estradiol concentrations were significantly increased after portal vein ligation, while the magnitude and delayed onset of increases in urinary total estrogen excretion suggested that this was due largely to increased estrogen production. In male rats, both castration (at 12 wk) and exogenous estrogen administration resulted in changes in hepatic cytochrome P450 levels and ethylmorphine N-demethylase activity that were qualitatively similar to those seen after portal vein ligation. In female and castrated male rats, however, cytochrome P450 was not affected by portal vein ligation. Testosterone supplementation corrected the changes of cytochrome P450 levels in castrated male rats did not have this effect in portal vein-ligated male rats. It is concluded that changes in sex hormone metabolism do occur after portal vein ligation and may contribute to alterations in cytochrome P450 and drug-metabolizing enzyme activity. Decreased levels of serum testosterone, however, do not alone account for the changes in hepatic drug metabolism in this model, and suppression of a hypothalamic-pituitary factor appears to be important.