Cyr61, a Member of the CCN Family, is Up-Regulated in Endometrium From Women With Polycystic Ovarian Syndrome Compared to Normal Controls

Abstract

ObjectiveTo evaluate the temporal and spatial distibution of Cyr61 in normal endometrium throughout the menstrual cycle and compare its expression in endometrium from women with polycystic ovarian syndrome (PCOS). We also studied the regulation of Cyr61 in the well-differentiated, hormone-responsive endometrial cell line, ECC1.DesignThis is a retrospective study on 21 endometrial samples from the proliferative and secretory phase of the menstrual cycle in normal women and women with hyperandrogenism and PCOS. Regulation of Cyr61 was performed in vitro using the well-differentiated endometrial cell line, ECC1.Materials and methodsWestern blot analysis of Cyr61 was performed on protein lysates of untreated ECC1 cells and cells treated for 6 and 12 hours with diethylstilbestrol (DES; 10-8M) in the presence or absence of the anti-estrogen ICI 182,780. Immunohistochemistry on endometrial samples and western blot analysis was performed using the specific Cyr61 polyclonal antibody (generously provided by Dr. Lester Lau, UIC, Chicago, IL). Additional staining was performed for the estrogen receptor alpha (ERa) and a marker of cell proliferation, Ki67. Twenty-one endometrial biopsies were obtained from both fertile and PCOS women during the menstrual cycle. Statistical analysis was performed using ANOVA with Bonferroni correction with significance at the 95% confidence interval (p < 0.05).ResultsConclusionThe Cyr61 protein is a sensitive marker of estrogen activity and is significantly increased in the endometrium of women with PCOS in both the proliferative and secretory phase. Further studies will be required to investigate the mechanism for this over-expression of Cyr61, but evidence suggests that failure of down-regulation of estrogen receptors in the secretory phase may play a role. ObjectiveTo evaluate the temporal and spatial distibution of Cyr61 in normal endometrium throughout the menstrual cycle and compare its expression in endometrium from women with polycystic ovarian syndrome (PCOS). We also studied the regulation of Cyr61 in the well-differentiated, hormone-responsive endometrial cell line, ECC1. To evaluate the temporal and spatial distibution of Cyr61 in normal endometrium throughout the menstrual cycle and compare its expression in endometrium from women with polycystic ovarian syndrome (PCOS). We also studied the regulation of Cyr61 in the well-differentiated, hormone-responsive endometrial cell line, ECC1. DesignThis is a retrospective study on 21 endometrial samples from the proliferative and secretory phase of the menstrual cycle in normal women and women with hyperandrogenism and PCOS. Regulation of Cyr61 was performed in vitro using the well-differentiated endometrial cell line, ECC1. This is a retrospective study on 21 endometrial samples from the proliferative and secretory phase of the menstrual cycle in normal women and women with hyperandrogenism and PCOS. Regulation of Cyr61 was performed in vitro using the well-differentiated endometrial cell line, ECC1. Materials and methodsWestern blot analysis of Cyr61 was performed on protein lysates of untreated ECC1 cells and cells treated for 6 and 12 hours with diethylstilbestrol (DES; 10-8M) in the presence or absence of the anti-estrogen ICI 182,780. Immunohistochemistry on endometrial samples and western blot analysis was performed using the specific Cyr61 polyclonal antibody (generously provided by Dr. Lester Lau, UIC, Chicago, IL). Additional staining was performed for the estrogen receptor alpha (ERa) and a marker of cell proliferation, Ki67. Twenty-one endometrial biopsies were obtained from both fertile and PCOS women during the menstrual cycle. Statistical analysis was performed using ANOVA with Bonferroni correction with significance at the 95% confidence interval (p < 0.05). Western blot analysis of Cyr61 was performed on protein lysates of untreated ECC1 cells and cells treated for 6 and 12 hours with diethylstilbestrol (DES; 10-8M) in the presence or absence of the anti-estrogen ICI 182,780. Immunohistochemistry on endometrial samples and western blot analysis was performed using the specific Cyr61 polyclonal antibody (generously provided by Dr. Lester Lau, UIC, Chicago, IL). Additional staining was performed for the estrogen receptor alpha (ERa) and a marker of cell proliferation, Ki67. Twenty-one endometrial biopsies were obtained from both fertile and PCOS women during the menstrual cycle. Statistical analysis was performed using ANOVA with Bonferroni correction with significance at the 95% confidence interval (p < 0.05). Results ConclusionThe Cyr61 protein is a sensitive marker of estrogen activity and is significantly increased in the endometrium of women with PCOS in both the proliferative and secretory phase. Further studies will be required to investigate the mechanism for this over-expression of Cyr61, but evidence suggests that failure of down-regulation of estrogen receptors in the secretory phase may play a role. The Cyr61 protein is a sensitive marker of estrogen activity and is significantly increased in the endometrium of women with PCOS in both the proliferative and secretory phase. Further studies will be required to investigate the mechanism for this over-expression of Cyr61, but evidence suggests that failure of down-regulation of estrogen receptors in the secretory phase may play a role.