大鼠肝脏的类固醇葡萄糖醛酸转移酶。雌酮和睾酮葡萄糖醛酸转移酶的特性以及卵巢切除、阉割和类固醇给药对这些酶的影响。

Steroid glucuronyltransferases of rat liver. Properties of oestrone and testosterone glucuronyltransferases and the effect of ovariectomy, castration and administration of steroids on the enzymes.

作者信息

Rao G S, Haueter G, Rao M L, Breuer H

出版信息

Biochem J. 1977 Mar 15;162(3):545-56. doi: 10.1042/bj1620545.

DOI:10.1042/bj1620545

PMID:869904

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1164637/

Abstract

Microsomal preparations from rat liver, kidney and intestine were tested for UDP-glucuronyltransferase activity by using oestrone, oestradiol-17 beta, oestriol, testosterone, cortisol, cortisone, corticosterone, aldosterone, tetrahydrocortisol and tetrahydrocortisone as substrates. The microsomal preparation from the liver glucuronidated oestrone, oestradiol-17 beta and testosterone. 2. The specific activity of the enzyme was significantly higher in livers from female rats than in those from male rats. 3. Testosterone was actively glucuronidated by both sexes. Cortisol, cortisone, corticosterone, aldosterone, tetrahydrocortisol and tetrahydrocortisone were not glucuronidated by any of the three tissues. 4. The non-ionic detergent Lubrol WX activates liver microsomal UDP-glucuronyltransferase 2-3-fold with oestrone and testosterone as substrates. 5. Oestrone glucuronyltransferase was inhibited by oestradiol-17 beta, predominantly competitively and by testosterone non-competitively. Bilirubin was a non-competitive inhibitor of oestrone glucuronidation. p-Nitrophenol had no effect. 6. Oestrone glucuronyltransferase could not be stimulated by either acute or prolonged treatment of animals with phenobarbital, whereas a single dose of 3-methylcholanthrene led to a moderate stimulation. 7. Ovariectomy leads to a 56% decrease in oestrone glucuronyltransferase activity; administration of oestradiol-17 beta induces the enzyme to normal activity after 12 days, and after 15 days the activity is twice the control value. Actinomycin D and cycloheximide block the oestradiol-17 beta-induced increase in enzyme activity. 8. Castration has no effect on the activity of testosterone glucuronyltransferase, nor does administration of testosterone influence enzyme activity. The results provide strong evidence for the existence of multiple steroid glucuronyltransferases in the liver of the rat.

摘要

以雌酮、雌二醇 -17β、雌三醇、睾酮、皮质醇、可的松、皮质酮、醛固酮、四氢皮质醇和四氢可的松为底物，检测大鼠肝脏、肾脏和肠道的微粒体制剂的UDP - 葡萄糖醛酸基转移酶活性。肝脏的微粒体制剂能使雌酮、雌二醇 -17β和睾酮葡萄糖醛酸化。2. 该酶的比活性在雌性大鼠肝脏中显著高于雄性大鼠肝脏。3. 两性的睾酮都能被积极地葡萄糖醛酸化。皮质醇、可的松、皮质酮、醛固酮、四氢皮质醇和四氢可的松均未被这三种组织中的任何一种葡萄糖醛酸化。4. 非离子去污剂Lubrol WX以雌酮和睾酮为底物时，可使肝脏微粒体UDP - 葡萄糖醛酸基转移酶活性提高2 - 3倍。5. 雌二醇 -17β对雌酮葡萄糖醛酸基转移酶有抑制作用，主要为竞争性抑制，而睾酮为非竞争性抑制。胆红素是雌酮葡萄糖醛酸化的非竞争性抑制剂。对硝基苯酚无作用。6. 苯巴比妥对动物进行急性或长期处理均不能刺激雌酮葡萄糖醛酸基转移酶，而单次给予3 - 甲基胆蒽可导致适度刺激。7. 卵巢切除导致雌酮葡萄糖醛酸基转移酶活性降低56%；给予雌二醇 -17β后12天，该酶活性诱导至正常水平，15天后活性是对照值的两倍。放线菌素D和环己酰亚胺可阻断雌二醇 -17β诱导的酶活性增加。8. 去势对睾酮葡萄糖醛酸基转移酶活性无影响，给予睾酮也不影响酶活性。这些结果为大鼠肝脏中存在多种类固醇葡萄糖醛酸基转移酶提供了有力证据。