Falany J L, Falany C N
Department of Pharmacology and Toxicology, University of Alabama, Birmingham, Alabama 35294, USA.
Endocrinology. 1996 Apr;137(4):1395-401. doi: 10.1210/endo.137.4.8625916.
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 (E2) with sulfate is thought to be an important mechanism in the regulation of the levels of active E2 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 E2 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 microns progesterone for 48 h resulted in a 7-fold increase in the sulfation of 20 nM E2. 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 E2, 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.
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微弱。β-雌二醇（E2）与硫酸盐的结合被认为是调节子宫内膜组织中活性E2水平的重要机制。据报道，在分泌期，由于卵巢分泌的高水平孕酮，雌激素硫酸化作用增强。雌激素磺基转移酶（hEST）是人类胞质磺基转移酶（ST）的一种独特形式，在低纳摩尔浓度下对E2和雌酮具有亲和力，最近已在哺乳动物细胞和细菌中克隆并表达（《类固醇生物化学与分子生物学杂志》52:529，1995年）。人类胞质ST的至少另外两种形式，脱氢表雄酮ST（hDHEA-ST）和酚-ST的酚硫酸化形式（hP-PST），也能使雌激素结合，但所需浓度为微摩尔级。本报告描述了孕酮对人子宫内膜腺癌Ishikawa细胞中hEST的特异性诱导作用，以此作为月经周期分泌期女性雌激素硫酸化增加的模型。用10微摩尔孕酮处理Ishikawa细胞48小时，导致20纳摩尔E2的硫酸化增加7倍。人脱氢表雄酮磺基转移酶（hDHEA-ST）和两种酚磺基转移酶（hP-PST、hM-PST）的选择性底物的硫酸化不受孕酮处理的影响。孕酮使Ishikawa细胞中免疫反应性hEST和hEST mRNA水平均升高，而免疫反应性hDHEA-ST、hP-PST和hM-PST水平未改变。用不同浓度的E2、睾酮或皮质醇处理Ishikawa细胞，未诱导出hEST活性。RU-486抑制了孕酮对hEST的诱导作用，表明孕酮是通过孕酮受体起作用的。这些结果表明，孕酮能够特异性诱导人Ishikawa腺癌细胞中的hEST和雌激素硫酸化，并提示了月经周期分泌期子宫内膜中雌激素硫酸化增加的一种机制。
