Effects of isoflavones or 17beta-estradiol on cell-matrix interactions in the endometrium of diabetic rats: relevance for hormone therapy

Abstract

Due to the symptoms that occur in postmenopausal women, even when they take hormone therapy, many women are insecure with the use of estrogens due to high risk of developing breast and/or endometrium cancer. This risk is potentiated when women are already predisposed or when they are making continuous use of another type of medicine. The diabetic rat model has been used thinking about postmenopausal women with diabetes who are afraid to use estrogens, so that an alternative treatment such as isoflavones would be appropriate. Another issue would be the possible effects of isoflavones in diabetic rats and whether they could resemble those of normal rats. Objective: To analyze the interactions between cells, matrix, differentiation, proliferation, adhesion, migration and angiogenesis, through analysis of the extracellular matrix in endometrium of diabetic rats treated with isoflavones or 17²-estradiol. Methods: 60 adult females rats (Rattus norvegicus albinos) at three months of age will be used. The animals will be divided into six (6) groups: GI (n = 10) control at estrous phase; GII (n = 10) control diabetic at the estrous phase; GIII (n = 10) control oophorectomized which will receive propylene glycol vehicle; GIV (n = 10) diabetic oophorectomized animals which will receive vehicle propylene glycol; GV (n = 10) diabetic oophorectomized animals which will receive soy isoflavones (150mg/Kg by gavage); GVI (n=10) diabetic oophorectomized animals which will receive estradiol, (10µg/Kg, subcutaneously). All animals will be treated for 30 consecutive days. At the end they will be anesthetized and then the endometrium removed and processed for molecular biology and immunohistochemistry assays. Part of the material will be plunged into nitrogen and destined for evaluation of the polymerase chain reaction (RT-PCR) chain to leucine-rich proteoglycans, and custom plate (PARN-013) for evaluation of adhesion molecules and extracellular matrix protein; other part will be dipped in acetone for determination of glycosaminoglycans and another part dipped in 10% formol for immunohistochemical detection of leucine-rich proteoglycans. For the analysis of results One-way ANOVA followed by Tukey-Kramer test will be used. Data whose p value was less than 5% (p d 0.05) will be considered statistically significant. The calculations should be done with SPSS, version 13 (SPSS, Chicago, IL). The results to be obtained should help to elucidate the role of extracellular matrix in the endometrium at postmenopausal age, especially in patients with diabetes. (AU)