Epoxide hydrolase affects estrogen production in the human ovary
Epoxide hydrolase affects estrogen production in the human ovary
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DOI：
10.1210/en.141.9.3353
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发表时间：
2000-09-01
期刊：
影响因子：
4.8
通讯作者：
Ueda, M
中科院分区：
文献类型：
--
作者：
Hattori, N;Fujiwara, H;Ueda, M
为了探讨卵巢细胞分化的机制，我们制备了一种新的单克隆抗体HCL-3，它与人黄体细胞反应。它也与人和猪肝细胞反应。从人黄体（CL）的免疫亲和纯化的HCL-3抗原被证明是一个46-kDa的蛋白质。从猪肝的46-kDa蛋白的N-末端22个氨基酸表现出较高的同源性（82%），人微粒体环氧化物水解酶（mEH）。从人CL或猪肝纯化的HCL-3抗原显示EH酶活性，证实HCL-3抗原与mEH相同，据报道mEH可使肝脏中的毒性底物解毒。在人类卵泡中，mEH在颗粒细胞和卵泡内膜细胞上被免疫化学检测到。在月经期和妊娠期的黄体中，mEH在大、小黄体细胞上也有表达。EH的竞争性抑制剂1，2-环氧-3，3，3-三氯丙烷抑制体外培养的颗粒细胞从睾酮转化雌二醇，表明mEH参与卵巢雌激素的产生。由于抗惊厥药丙戊酸钠及其类似物可抑制EH酶活性，因此这些发现为了解服用抗惊厥药的癫痫患者中常见的内分泌疾病病因提供了新的见解。
To investigate the mechanisms of ovarian cell differentiation, we raised a new monoclonal antibody, HCL-3, which reacted with human luteal cells. It also reacted with human and porcine hepatocytes. The immunoaffinity-purified HCL-3 antigen from human corpora lutea (CL) was shown to be a 46-kDa protein. The N-terminal 22 amino acids of the 46-kDa protein from porcine liver exhibited high homology (82%) to human microsomal epoxide hydrolase (mEH). The purified HCL-3 antigen from human CL or porcine liver showed EH enzyme activity, confirming that HCL-3 antigen is identical to mEH, which is reported to detoxify the toxic substrates in the liver. In human follicles, mEH was immunohistochemically detected on granulosa and theca interna cells. In the menstrual and pregnant CL, mEH was also expressed on large and small luteal cells. A competitive inhibitor of EH, 1,2-epoxy-3,3,3-trichloropropane, inhibited the conversion of estradiol from testosterone by granulosa cells cultured in vitro, indicating the involvement of mEH in ovarian estrogen production. Because anticonvulsant sodium valproate and its analogues were reported to inhibit EH enzyme activity, these findings provide a new insight into the etiology of endocrine disorders that are frequently observed among epileptic patients taking anticonvulsant drugs.