Regulation of estrogen sulfotransferase in human endometrial adenocarcinoma cells by progesterone
Regulation of estrogen sulfotransferase in human endometrial adenocarcinoma cells by progesterone
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DOI：
10.1210/en.137.4.1395
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发表时间：
1996-04-01
期刊：
影响因子：
4.8
通讯作者：
Falany, CN
中科院分区：
文献类型：
--
作者：
Falany, JL;Falany, CN
在人类月经周期的分泌期，子宫内膜对卵巢分泌的雌激素反应最小。β-雌二醇（E（2））与硫酸结合被认为是调节子宫内膜组织中活性E（2）水平的重要机制。据报道，雌激素硫酸化在分泌期增加，以响应卵巢分泌的高水平孕酮。雌激素磺基转移酶（hEST），一种在低纳摩尔浓度下对E（2）和雌酮具有亲和力的人胞质磺基转移酶（ST）的独特形式，最近已被克隆并在哺乳动物细胞和细菌中表达（J Steroid Biochem Mol Biol 52：529，1995）。至少两种其他形式的人胞质ST，脱氢表雄酮ST（hDHEA-ST）和苯酚-ST的苯酚硫酸化形式（hP-PST），也结合雌激素，但在微摩尔浓度。这份报告描述了特定的诱导hEST在人类石川子宫内膜腺癌细胞的孕激素作为一个模型的增加雌激素硫酸化观察妇女在月经周期的分泌期。用10 μ M孕酮处理石川细胞48小时，导致20 nM E的硫酸化增加7倍（2）。人脱氢表雄酮磺基转移酶（hDHEA-ST）和两种形式的苯酚磺基转移酶（hP-PST，hM-PST）的选择性底物的硫酸化不受孕酮处理的影响。孕酮可使石川细胞hEST和hESTmRNA表达水平升高，而hDHEA-ST、hP-PST和hM-PST表达水平无明显变化。用不同浓度的E（2）、睾酮或皮质醇处理石川细胞不能诱导hEST活性。孕酮对hEST的诱导作用可被RU-486抑制，表明孕酮通过孕酮受体起作用。这些结果表明，孕激素是能够特异性地诱导hEST和雌激素硫酸化的人石川腺癌细胞，并提出了一种机制，增加雌激素硫酸化的子宫内膜在月经周期的分泌期。
During the secretory phase of the human menstrual cycle, the endometrium is minimally responsive to the estrogens secreted from the ovaries. Conjugation of beta-estradiol (E(2)) with sulfate is thought to be an important mechanism in the regulation of the levels of active E(2) in endometrial tissue. Estrogen sulfation is reportedly increased during the secretory phase in response to the high levels of progesterone secreted by the ovaries. Estrogen sulfotransferase (hEST), a distinct form of human cytosolic sulfotransferase (ST) with an affinity for E(2) and estrone at low nanomolar concentrations, has recently been cloned and expressed in mammalian cells and in bacteria (J Steroid Biochem Mol Biol 52:529, 1995). At least two other forms of human cytosolic ST, dehydroepiandrosterone ST (hDHEA-ST) and the phenol-sulfating form of phenol-ST (hP-PST), also conjugate estrogens but at micromolar concentrations. This report describes the specific induction of hEST in human Ishikawa endometrial adenocarcinoma cells by progesterone as a model for the increases in estrogen sulfation observed in women during the secretory phase of the menstrual cycle. Treatment of Ishikawa cells with 10 mu M progesterone for 48 h resulted ina 7-fold increase in the sulfation of 20 nM E(2). The sulfation of selective substrates for human dehydroepiandrosterone sulfotransferase (hDHEA-ST) and the two forms of phenol sulfotransferase (hP-PST, hM-PST) were not affected by treatment with progesterone. The levels of immunoreactive hEST and hEST mRNA in the Ishikawa cells were both increased by progesterone, whereas the levels of immunoreactive hDHEA-ST, hP-PST, and hM-PST were not altered. hEST activity was not induced by treatment of Ishikawa cells with varying concentrations of E(2), testosterone, or cortisol. The induction of hEST by progesterone was inhibited by RU-486, indicating that progesterone is acting via the progesterone receptor. These results indicate that progesterone is capable of specifically inducing hEST and estrogen sulfation in human Ishikawa adenocarcinoma cells and suggest a mechanism for increasing estrogen sulfation in the endometrium during the secretory phase of the menstrual cycle.