title: Effects of genistein in combination with conjugated estrogens on endometrial hyperplasia and metabolic dysfunction in ovariectomized mice.
abstract: 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.
authors: Department of Food and Biotechnology, Korea University, Sejong, 339-700, South Korea.
authors: Jun Ho
authors: JH
authors: Kim
authors: Young Jun
authors: YJ
authors: Kim
mesh_terms: D050154:Adiposity / Q000187:drug effects; D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects; D019587:Dietary Supplements / Q000009:adverse effects; D004714:Endometrial Hyperplasia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015914:Estrogen Replacement Therapy / Q000009:adverse effects; D004967:Estrogens / Q000009:adverse effects / Q000627:therapeutic use; D004966:Estrogens, Conjugated (USP) / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D019833:Genistein / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018149:Glucose Intolerance / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D010052:Ovariectomy / Q000009:adverse effects; D050177:Overweight / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D048789:Phytoestrogens / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D020849:Raloxifene Hydrochloride / Q000009:adverse effects / Q000627:therapeutic use; D011897:Random Allocation; D020845:Selective Estrogen Receptor Modulators / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D048789:Phytoestrogens; D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride; D019833:Genistein