Changes in levels of urinary estrogen metabolites after oral indole-3-carbinol treatment in humans
Changes in levels of urinary estrogen metabolites after oral indole-3-carbinol treatment in humans
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DOI：
10.1093/jnci/89.10.718
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发表时间：
1997-05-21
影响因子：
10.3
通讯作者：
Bradlow, HL
中科院分区：
文献类型：
--
作者：
Michnovicz, JJ;Adlercreutz, H;Bradlow, HL
工作背景：人体内雌激素的氧化代谢主要由细胞色素P450介导，其许多同工酶可由饮食和药理学试剂诱导。一个主要途径，2-羟基化，由饮食吲哚-3-甲醇（I3 C）诱导，其存在于十字花科蔬菜（例如，卷心菜和花椰菜）。目的：由于所有途径可用的雌激素底物库有限，我假设雌激素霉菌的2-羟基化增加导致竞争代谢途径的活性降低。方法：在口服I3 C之前和之后收集受试者的尿液样品（6-7 mg/kg/天），在第一项研究中，7名男性接受I3 C 1周;在第二项研究中，10名妇女接受了2个月的I3 C，通过气相色谱-质谱法测量了每个样本中13种雌激素的分布，结果：在男性和女性中，I3 C显著增加了C-2雌激素的尿排泄。I3 C治疗后，几乎所有其他雌激素代谢产物的尿浓度，包括雌二醇、雌酮、雌三醇和16 α-羟基雌酮的水平均降低。这些发现支持I3 C诱导的雌激素2-羟基化导致已知激活雌激素受体的几种代谢物浓度降低的假设，这种影响可能会降低女性的雌激素刺激，影响：I3 C可能对人类乳腺癌有化学预防活性，尽管女性儿茶酚雌激素水平较高的长期影响需要进一步研究。
Background: The oxidative metabolism of estrogens in humans is mediated primarily by cytochrome P450, many isoenzymes of which are inducible by dietary and pharmacologic agents, One major pathway, 2-hydroxylation, is induced by dietary indole-3-carbinol (I3C), which is present in cruciferous vegetables (e.g., cabbage and broccoli). Purpose: Because the pool of available estrogen substrates for all pathways is limited, me hypothesized that increased 2-hydroxylation of estrogens mould lead to decreased activity in competing metabolic pathways, Methods: Urine samples were collected from subjects before and after oral ingestion of I3C (6-7 mg/kg per day), In the first study, seven men received I3C for 1 week; in the second study, 10 women received I3C for 2 months, A profile of 13 estrogens was measured in each sample by gas chromatography-mass spectrometry, Results: In both men and women, I3C significantly increased the urinary excretion of C-2 estrogens, The urinary concentrations of nearly all other estrogen metabolites, including levels of estradiol, estrone, estriol, and 16 alpha-hydroxyestrone, were lower after I3C treatment, Conclusions: These findings support the hypothesis that I3C-induced estrogen 2-hydroxylation results in decreased concentrations of several metabolites known to activate the estrogen receptor, This effect may lower estrogenic stimulation in women, Implications: I3C may have chemopreventive activity against breast cancer in humans, although the long-term effects of higher catechol estrogen levels in women require further investigation.