Liddle C, Murray M, Farrell G C
Department of Medicine, University of Sydney, Westmead Hospital, NSW, Australia.
Gastroenterology. 1989 Mar;96(3):864-72.
Partial hepatectomy in male adult rats results in raised serum estrogen levels and demasculinization of certain aspects of hepatic metabolism. Some constitutive forms of hepatic cytochrome P450 are sex-dependent and we have previously demonstrated demasculinization of cytochrome P450 isozyme distribution in a rat model of cirrhosis. As liver regeneration is an integral component of cirrhosis, the present study was performed to ascertain the effects of regeneration on hepatic cytochrome P450 isozyme composition and serum sex steroid concentrations. Adult male rats were subjected to 65% partial hepatectomy or sham-operation. The position-specific hydroxylation of androstenedione was used as a probe for isozyme activity. Serum sex steroids, hepatic enzymes, and hepatic deoxyribonucleic acid synthesis were measured in groups of animals at 0, 6, 24, 48, and 72 h. By 72 h total microsomal cytochrome P450 in partially hepatectomized animals had fallen to 66% of that in nonoperated animals. In both partially hepatectomized and sham-operated animals, androstenedione 7 alpha- and 16 beta-hydroxylase activity returned to preoperative levels by 48 h. However, the male-specific androstenedione 16 alpha- and 6 beta-hydroxylase activities and aromatase activity remained suppressed in partially hepatectomized liver. Serum estradiol increased eightfold in partially hepatectomized rats and peaked at 6 h followed by a gradual fall to control values. No change in serum estradiol was observed in sham-operated animals. We conclude that demasculinization of hepatic oxidative metabolism occurs in regenerating rat liver. The early rise in serum estradiol is consistent with a role for this hormone in the changes in cytochrome P450 observed, and possibly the process of liver regeneration.
成年雄性大鼠部分肝切除术后，血清雌激素水平升高，肝脏代谢的某些方面出现去雄性化。肝脏细胞色素P450的一些组成形式具有性别依赖性，我们之前在肝硬化大鼠模型中证实了细胞色素P450同工酶分布的去雄性化。由于肝再生是肝硬化的一个重要组成部分，本研究旨在确定再生对肝脏细胞色素P450同工酶组成和血清性类固醇浓度的影响。成年雄性大鼠接受65%部分肝切除术或假手术。将雄烯二酮的位置特异性羟基化用作同工酶活性的探针。在术后0、6、24、48和72小时对动物组进行血清性类固醇、肝酶和肝脱氧核糖核酸合成的检测。到72小时时，部分肝切除动物的总微粒体细胞色素P450降至未手术动物的66%。在部分肝切除和假手术动物中，雄烯二酮7α-和16β-羟化酶活性在48小时时恢复到术前水平。然而，部分肝切除肝脏中雄性特异性的雄烯二酮16α-和6β-羟化酶活性以及芳香化酶活性仍然受到抑制。部分肝切除大鼠的血清雌二醇增加了八倍，在6小时达到峰值，随后逐渐降至对照值。假手术动物的血清雌二醇未观察到变化。我们得出结论，再生大鼠肝脏中发生了肝脏氧化代谢的去雄性化。血清雌二醇的早期升高与该激素在观察到的细胞色素P450变化中所起的作用一致，并且可能与肝再生过程有关。
