Markaverich B M, Webb B, Densmore C L, Gregory R R
Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Environ Health Perspect. 1995 Jun;103(6):574-81. doi: 10.1289/ehp.95103574.
Isoflavonoids and related compounds such as coumestrol have classically been categorized as phytoestrogens because these environmentally derived substances bind to the estrogen receptor (ER) and increase uterine wet weight in immature rats and mice. Assessment of the binding affinities of isoflavonoids for ER and subsequent effects on uterine growth suggest these compounds are less active estrogens than estradiol and therefore may reduce the risk of developing breast or prostate cancer in humans by preventing estradiol binding to ER. With the renewed interest in the relationships between environmental estrogens and cancer cause and prevention, we assessed the effects of the phytoestrogen coumestrol on uterotropic response in the immature, ovariectomized rat. Our studies demonstrated that in this animal model, coumestrol is an atypical estrogen that does not stimulate uterine cellular hyperplasia. Although acute (subcutaneous injection) or chronic (multiple injection or orally via drinking water) administration of coumestrol significantly increased uterine wet and dry weights, the phytoestrogen failed to increase uterine DNA content. The lack of true estrogenic activity was characterized by the inability of this phytoestrogen to cause cytosolic ER depletion, nuclear ER accumulation, or the stimulation of nuclear type II sites which characteristically precede estrogenic stimulation of cellular DNA synthesis and proliferation. In fact, subcutaneous or oral coumestrol treatment caused an atypical threefold induction of cytosolic ER without corresponding cytosolic depletion and nuclear accumulation of this receptor, and this increased the sensitivity of the uterus to subsequent stimulation by estradiol.(ABSTRACT TRUNCATED AT 250 WORDS)
异黄酮类化合物及相关化合物如香豆雌酚，传统上被归类为植物雌激素，因为这些来源于环境的物质能与雌激素受体（ER）结合，并增加未成熟大鼠和小鼠的子宫湿重。对异黄酮类化合物与ER的结合亲和力及其对子宫生长后续影响的评估表明，这些化合物作为雌激素的活性低于雌二醇，因此可能通过阻止雌二醇与ER结合来降低人类患乳腺癌或前列腺癌的风险。随着对环境雌激素与癌症发生及预防之间关系的重新关注，我们评估了植物雌激素香豆雌酚对未成熟去卵巢大鼠子宫促生长反应的影响。我们的研究表明，在这种动物模型中，香豆雌酚是一种非典型雌激素，不会刺激子宫细胞增生。尽管香豆雌酚的急性（皮下注射）或慢性（多次注射或通过饮水口服）给药显著增加了子宫的湿重和干重，但这种植物雌激素未能增加子宫DNA含量。这种植物雌激素无法导致胞质ER耗竭、核ER积累，也无法刺激核II型位点，而这些通常是雌激素刺激细胞DNA合成和增殖之前的特征性表现，这表明它缺乏真正的雌激素活性。事实上，皮下或口服香豆雌酚治疗导致胞质ER非典型地增加了三倍，而该受体没有相应的胞质耗竭和核积累，这增加了子宫对随后雌二醇刺激的敏感性。（摘要截选至250字）
