Cotroneo M S, Lamartiniere C A
Department of Pharmacology and Toxicology and the Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Toxicol Sci. 2001 May;61(1):68-75. doi: 10.1093/toxsci/61.1.68.
Endometriosis is a disease in which uterine tissue proliferates in extrauterine sites. Using a surgical model to simulate endometriosis, we explored the potential for the phytoestrogen genistein, by injection and diet, to sustain endometriosis in rats. Uterine tissue was attached to intestinal mesentery of 8-week-old Sprague Dawley rats. After 3 weeks, the rats were ovariectomized and the implants measured. Following 3 weeks of daily injections or exposure to dietary genistein, animals were necropsied and implants located and measured. Injections of genistein (50 and 16.6 microg/g BW) or estrone (1 microg/rat) sustained the implants; injection of sesame oil (vehicle for estrone), dimethylsulfoxide (DMSO; vehicle for genistein), or genistein at 5.0 microg/g BW did not sustain implants. Dietary genistein (250 or 1000 mg genistein/kg AIN-76A diet) did not support the implants. In ovary-intact rats exposed to 250 mg genistein/kg AIN-76A diet, implant size was not altered, compared to control-fed animals. To assess estrogenic actions of genistein, we measured uterine estrogen receptor alpha (ER-alpha) and progesterone receptor (PR) isoforms A and B by Western blot analyses. Injections of estrone or genistein (50 or 16.6 microg/g BW) significantly reduced uterine ER-alpha compared to vehicle-treated animals. PR (B) was significantly increased by all injected doses of genistein or estrone and by the higher dietary dose (1000 mg genistein/kg AIN-76A). PR (A) was significantly increased by injected doses of genistein (16.6 and 5.0 microg/g BW). We conclude that pharmacologic injections, but not dietary physiological concentrations of genistein, support surgically induced endometriosis in rats. Our results suggest a critical role for ER modulation and genistein bioavailability in the maintenance of the implants.
子宫内膜异位症是一种子宫组织在子宫外部位增殖的疾病。我们使用一种手术模型来模拟子宫内膜异位症，通过注射和饮食的方式，探究植物雌激素染料木黄酮维持大鼠子宫内膜异位症的可能性。将子宫组织附着于8周龄的斯普拉格-道利大鼠的肠系膜上。3周后，对大鼠进行卵巢切除并测量植入物。在每日注射或摄入含染料木黄酮的饮食3周后，对动物进行尸检，定位并测量植入物。注射染料木黄酮（50和16.6微克/克体重）或雌酮（1微克/只大鼠）可维持植入物；注射芝麻油（雌酮的溶媒）、二甲基亚砜（DMSO；染料木黄酮的溶媒）或5.0微克/克体重的染料木黄酮则不能维持植入物。含染料木黄酮的饮食（250或1000毫克染料木黄酮/千克AIN - 76A饮食）不能维持植入物。在摄入250毫克染料木黄酮/千克AIN - 76A饮食的未切除卵巢的大鼠中，与喂食对照饮食的动物相比，植入物大小未改变。为了评估染料木黄酮的雌激素作用，我们通过蛋白质印迹分析测量子宫雌激素受体α（ER - α）以及孕激素受体（PR）的A和B亚型。与溶媒处理的动物相比，注射雌酮或染料木黄酮（50或16.6微克/克体重）可显著降低子宫ER - α。所有注射剂量的染料木黄酮或雌酮以及较高饮食剂量（1000毫克染料木黄酮/千克AIN - 76A）均可使PR（B）显著增加。注射剂量的染料木黄酮（16.6和5.0微克/克体重）可使PR（A）显著增加。我们得出结论，药理学注射而非饮食生理浓度的染料木黄酮可维持大鼠手术诱导的子宫内膜异位症。我们的结果表明ER调节和染料木黄酮生物利用度在维持植入物方面起关键作用。
