Profiles of bile acids and progesterone metabolites in the urine and serum of women with intrahepatic cholestasis of pregnancy
Profiles of bile acids and progesterone metabolites in the urine and serum of women with intrahepatic cholestasis of pregnancy
复制标题
DOI：
10.1016/s0168-8278(97)80181-x
复制
发表时间：
1997-08-01
影响因子：
25.7
通讯作者：
Sjovall, J
中科院分区：
文献类型：
--
作者：
Meng, LJ;Reyes, H;Sjovall, J
背景/目的和方法：妊娠期肝内胆汁淤积（ICP）的病因尚不清楚。我们对 6 名患者血清和尿液中的孕酮代谢物和胆汁酸进行了全面的色谱和质谱分析，以表征可能对疾病发展具有重要意义的变化。结果：ICP 患者血清和尿液中的结合胆汁酸增加，而健康妊娠和 ICP 中非结合胆汁酸的水平相似。在健康妊娠和ICP中，未结合和结合的7α,12α-二羟基-3-氧代-4-胆烯酸均通过尿液排出，这可能表明妊娠期间3-氧代-Delta(4)-类固醇5β-还原酶的速率限制。 ICP中总硫酸化黄体酮代谢物的血清水平和尿排泄增加，而葡萄糖醛酸苷不变或较低，证实了先前的结果，具有3α-羟基-5α(H)构型的代谢物的分数增加。 ICP 中 5 α-孕烷-3 α、20 α-二醇 3-硫酸酯、20-N-乙酰氨基葡萄糖的尿排泄量大大增加，3 α-羟基-5 α-雄甾烷-17 β-羧酸（被认为是孕酮代谢物）的尿排泄量也大大增加。结论：本研究和之前研究的综合结果与孕酮还原代谢的主要变化相一致。 ICP，导致具有 3 α-羟基-5 α(H) 构型的代谢物和更大比例的硫酸盐的形成增加。硫酸化代谢物（特别是二硫酸盐）的胆汁分泌似乎也存在选择性缺陷。
Background/Aims and Methods: The etiology of intrahepatic cholestasis of pregnancy (ICP) is unknown. We have performed comprehensive chromatographic and mass spectrometric analyses of progesterone metabolites and bile acids in serum and urine of six patients in order to characterize changes that might be of importance for the development of the disease.Results: Conjugated bile acids were increased in serum and urine of patients with ICP while the levels of unconjugated bile acids were similar in healthy pregnancies and ICP. Unconjugated and conjugated 7 alpha,12 alpha-dihydroxy-3-oxo-4-cholenoic acid was excreted in urine both in healthy pregnancies and in ICP, possibly indicating a rate limitation of 3-oxo-Delta(4)-steroid 5 beta-reductase in pregnancy. The serum levels and urinary excretion of total sulfated progesterone metabolites were increased in ICP while the glucuronides were unchanged or low confirming previous results, the fraction of metabolites with 3 alpha-hydroxy-5 alpha(H) configuration was increased. The urinary excretion of 5 alpha-pregnane-3 alpha,20 alpha-diol 3-sulfate,20-N-acetylglucosaminide was greatly increased in ICP, as was that of 3 alpha-hydroxy-5 alpha-androstane-17 beta-carboxylic acid, assumed to be a progesterone metabolite.Conclusions: The combined results of this and previous studies are compatible with a primary change in the reductive metabolism of progesterone in ICP, resulting in increased formation of metabolites with a 3 alpha-hydroxy-5 alpha(H) configuration and a larger fraction of sulfates. There also seems to be a selective defect in the biliary secretion of sulfated metabolites, particularly disulfates.