Role of sulfate conjugation in estrogen metabolism and activity.
Role of sulfate conjugation in estrogen metabolism and activity.
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硫酸盐结合在雌激素代谢和活性中的作用。
DOI：
10.1080/15287397809529662
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发表时间：
1978
期刊：
影响因子：
--
通讯作者：
D. V. Singh
中科院分区：
文献类型：
--
作者：
S. Brooks;J. Rozhin;B. Pack;L. Horn;V. Godefroi;E. Locke;J. Žemlička;D. V. Singh
雌激素的硫酸盐结合物作为甾体激素体内平衡和活性的重要代谢产物，越来越受到人们的关注。在女性中，已知硫酸雌激素是源自卵巢分泌和肝脏代谢的血浆的主要成分。然而，直到最近才证明在雌激素靶组织中有硫酸化雌激素的能力。猪子宫雌激素磺基转移酶只有在第一个完整的发情周期后才出现。青春期后，母猪子宫内雌激素的磺基化在间情期非常活跃，而雌激素磺基转移酶在发情期不存在。猪和人子宫内雌激素磺酰化的循环与血浆孕酮水平直接相关。啮齿类动物和人类乳腺肿瘤在类固醇醇和雌激素磺基转移酶中也高度活跃。与子宫磺基转移酶不同，这些酶显然受到卵巢切除术后出现的因素的刺激。雌激素在靶组织中的作用机制尚不清楚。然而，最近的研究表明，子宫内膜雌激素硫酸化的周期性变化可能控制17 β-雌二醇对细胞质受体的可用性。这一前提得到了受精后备母猪和经产母猪着床期间持续高雌激素磺酰化活性和低核受体水平的支持。利用纯化的牛肾上腺磺基转移酶，底物和抑制剂的要求，确定这种酶。还可以设计一种特异性抑制剂，其将阻断雌激素磺酰化而不干扰生理水平的17 β-雌二醇的受体结合和核迁移。这种抑制剂，3-甲氧基-4-硝基雌酮，将有助于建立子宫和乳房雌激素硫酸化的作用。
There has been an increasing interest in the sulfate conjugates of estrogens as important metabolites in steroid hormone homeostasis and activity. In women estrogen sulfates have been known as major components of plasma originating from ovarian secretion and hepatic metabolism. However, only recently has the capacity to sulfurylate estrogens been demonstrated in estrogen target tissues. Porcine uterus estrogen sulfotransferase appears only after the first complete estrous cycle. Following puberty, gilt uterine sulfurylation of estrogens is extremely active during diestrus, whereas estrogen sulfotransferase is not present during estrus. This cycling of estrogen sulfurylation in porcine and human uteri can be related directly to plasma progesterone levels. Rodent and human mammary tumors are also highly active in both steroid alcohol and estrogen sulfotransferases. Unlike uterine sulfotransferases, these enzymes are apparently stimulated by factors that appear following ovariectomy. The function of estrogen sulfurylation by target tissues remains obscure. However, recent investigations have indicated that the cyclic variation in endometrial estrogen sulfurylation may control the availability of 17 beta-estradiol to the cytoplasmic receptor. This premise is supported by the continued high estrogen sulfurylation activity and low nuclear receptor levels during implantation in fertilized gilts and sows. Utilizing purified bovine adrenal sulfotransferase, the substrate and inhibitor requirements were determined for this enzymes. It was also possible to design a specific inhibitor that will block estrogen sulfurylation without interfering with the receptor binding and nuclear migration of physiological levels of 17 beta-estradiol. This inhibitor, 3-methoxy-4-nitroestrone, will help in establishing the role of uterine and mammary estrogen sulfurylation.