title: The role of androst-5-ene-3β,17β-diol (androstenediol) in cell proliferation in endometrium of women with polycystic ovary syndrome.
abstract: Women with polycystic ovary syndrome (PCOS) show high prevalence of endometrial hyperplasia and adenocarcinoma. Endometrial proliferation is increased, evaluated by high levels of Ki67 (cell cycle marker) and low levels of p27 (negative regulator of cell cycle). Nevertheless, endometrial changes in cyclin D1 (positive regulator of cell cycle) in PCOS-women are not described. Androst-5-ene-3β,17β-diol (androstenediol), steroid with estrogenic activity present in endometria, could be related to increased endometrial cell proliferation. The objective of this study was to determine protein content of cyclin D1 and androstenediol levels in endometria from PCOS and control-women and to evaluate the possible mechanism favoring cell proliferation associated with hormonal characteristics of patients. Therefore, cyclin D1 protein content in PCOS-women and control-endometrial tissue were assessed by western blot and immunohistochemistry. The androstenediol levels were evaluated by ELISA. To further analyze the effect of steroids (androstenediol, 17β-estradiol, testosterone) in cell proliferation, levels of proteins cyclin D1, p27 and Ki67 were evaluated in an in vitro model of stromal endometrial cells T-HESC and St-T1b. An increase in cyclin D1 and androstenediol was observed in tissues from PCOS-women relative to control group (p<0.05). In the in vitro model, androstenediol exerted increase in cyclin D1 (p<0.05) and a decrease in p27 protein level (p<0.05), while Ki67 in St-T1b cells increased under this stimulus (p<0.05). Testosterone produces opposite effects in the levels of the above markers (p<0.05). Therefore, the hormonal imbalance associated with this syndrome could alter endometrial tissue homeostasis, promoting cell proliferation. Androstenediol is a molecule that could be involved by stimulating proliferation, whereas testosterone elicits a role of cell cycle repressor.
authors: Department of Obstetrics and Gynecology, School of Medicine, University of Chile, Clinical Hospital, Santos Dumont # 999, Santiago, Chile.
authors: Francisca
authors: F
authors: Plaza-Parrochia
authors: Department of Obstetrics and Gynecology, School of Medicine, University of Chile, Clinical Hospital, Santos Dumont # 999, Santiago, Chile.
authors: Ketty
authors: K
authors: Bacallao
authors: Department of Obstetrics and Gynecology, School of Medicine, University of Chile, Clinical Hospital, Santos Dumont # 999, Santiago, Chile.
authors: Cristian
authors: C
authors: Poblete
authors: Department of Pathology, School of Medicine, University of Chile, San Borja Arriarán Clinical Hospital, Santa Rosa #1234, Chile.
authors: Fernando
authors: F
authors: Gabler
authors: Department of Obstetrics and Gynecology, School of Medicine, University of Chile, Clinical Hospital, Santos Dumont # 999, Santiago, Chile.
authors: Rodrigo
authors: R
authors: Carvajal
authors: Department of Obstetrics and Gynecology, School of Medicine, University of Chile, Clinical Hospital, Santos Dumont # 999, Santiago, Chile.
authors: Carmen
authors: C
authors: Romero
authors: Institute of Nutrition and Food Technology, University of Chile, Macul #5540, Chile.
authors: Luis
authors: L
authors: Valladares
authors: Department of Obstetrics and Gynecology, School of Medicine, University of Chile, Clinical Hospital, Santos Dumont # 999, Santiago, Chile. Electronic address: mvega@med.uchile.cl.
authors: Margarita
authors: M
authors: Vega
mesh_terms: D000328:Adult; D015114:Androstenediol / Q000378:metabolism*; D000735:Androstenedione / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D019938:Cyclin D1 / Q000378:metabolism; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D011085:Polycystic Ovary Syndrome / Q000378:metabolism* / Q000473:pathology; D011374:Progesterone / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism
chemical_list: C530104:CCND1 protein, human; D018809:Proliferating Cell Nuclear Antigen; C413374:p27 antigen; D019938:Cyclin D1; D013739:Testosterone; D000735:Androstenedione; D011374:Progesterone; D015114:Androstenediol
keywords: Androstenediol; Cyclin D1; Endometria; Estrogens; PCOS; p27