Kim Jun Ho, Kim Young Jun
Department of Food and Biotechnology, Korea University, Sejong, 339-700, South Korea.
Endocr J. 2015;62(6):531-42. doi: 10.1507/endocrj.EJ15-0056. Epub 2015 Apr 15.
Tissue-selective estrogen complex (TSEC), which combines a selective estrogen receptor modulator (SERM) with one or more estrogens, is a novel approach to menopausal therapy. It has been demonstrated that the phytoestrogen genistein (GEN) exhibits mixed estrogen receptor agonist and antagonist activity, suggesting that GEN may have potential for use as a natural SERM. We evaluated, for the first time, the effects of GEN, conjugated estrogens (CE), and their pairing effects as a TSEC treatment on estrogen-induced endometrial hyperplasia and metabolic dysfunction in ovariectomized (OVX) mice fed a high-fat diet. CE replacement prevented fat accumulation in the adipose tissue and liver, improved glucose homeostasis, and induced endometrial hyperplasia in OVX mice. GEN at 100 mg/kg showed CE mimetic effects in preventing ovariectomy-induced metabolic dysfunctions without endometrial stimulation. Combination treatments with CE and GEN prevented metabolic dysfunctions more strongly than CE alone, but at both low and high doses, GEN did not reverse CE-induced endometrial hyperplasia. In addition, we found that in a TSEC regimen, a typical SERM raloxifene maintains the metabolic benefits of CE while simultaneously protecting the endometrium in OVX mice. These findings indicate that GEN acts as an estrogen agonist in metabolic regulation, but has no SERM function in the uteri of OVX mice.
组织选择性雌激素复合物（TSEC）将选择性雌激素受体调节剂（SERM）与一种或多种雌激素结合，是一种治疗更年期的新方法。已证明植物雌激素染料木黄酮（GEN）具有雌激素受体激动剂和拮抗剂的混合活性，这表明GEN可能有作为天然SERM的潜力。我们首次评估了GEN、结合雌激素（CE）及其作为TSEC治疗对喂食高脂饮食的去卵巢（OVX）小鼠雌激素诱导的子宫内膜增生和代谢功能障碍的影响。CE替代可防止脂肪在脂肪组织和肝脏中积累，改善葡萄糖稳态，并在OVX小鼠中诱导子宫内膜增生。100mg/kg的GEN在预防去卵巢诱导的代谢功能障碍方面显示出CE模拟效应，而不会刺激子宫内膜。CE和GEN联合治疗比单独使用CE更能有效预防代谢功能障碍，但无论低剂量还是高剂量，GEN都不能逆转CE诱导的子宫内膜增生。此外，我们发现在TSEC方案中，一种典型的SERM雷洛昔芬在维持CE对代谢的有益作用的同时，还能保护OVX小鼠的子宫内膜。这些发现表明，GEN在代谢调节中起雌激素激动剂的作用，但在OVX小鼠子宫中没有SERM功能。
