title: Molecular characterization of insulin resistance and glycolytic metabolism in the rat uterus.
abstract: Peripheral insulin resistance and hyperandrogenism are the primary features of polycystic ovary syndrome (PCOS). However, how insulin resistance and hyperandrogenism affect uterine function and contribute to the pathogenesis of PCOS are open questions. We treated rats with insulin alone or in combination with human chorionic gonadotropin (hCG) and showed that peripheral insulin resistance and hyperandrogenism alter uterine morphology, cell phenotype, and cell function, especially in glandular epithelial cells. These defects are associated with an aberration in the PI3K/Akt signaling pathway that is used as an indicator for the onset of insulin resistance in classical metabolic tissues. Concomitantly, increased GSK3β (Ser-9) phosphorylation and decreased ERK1/2 phosphorylation in rats treated with insulin and hCG were also observed. We also profiled the expression of glucose transporter (Glut) isoform genes in the uterus under conditions of insulin resistance and/or hyperandrogenism. Finally, we determined the expression pattern of glycolytic enzymes and intermediates during insulin resistance and hyperandrogenism in the uterus. These findings suggest that the PI3K/Akt and MAPK/ERK signaling pathways play a role in the onset of uterine insulin resistance, and they also suggest that changes in specific Glut isoform expression and alterations to glycolytic metabolism contribute to the endometrial dysfunction observed in PCOS patients.
authors.affiliation: Department of Obstetrics and Gynecology, Key Laboratory and Unit of Infertility in Chinese Medicine, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, 150040 Harbin, China.|Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden.
authors.forename: Yuehui
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, Key Laboratory and Unit of Infertility in Chinese Medicine, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, 150040 Harbin, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Obstetrics and Gynecology, Key Laboratory and Unit of Infertility in Chinese Medicine, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, 150040 Harbin, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Obstetrics and Gynecology, Key Laboratory and Unit of Infertility in Chinese Medicine, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, 150040 Harbin, China.
authors.forename: Fanci
authors.initials: F
authors.lastname: Meng
authors.affiliation: Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden.
authors.forename: Min
authors.initials: M
authors.lastname: Hu
authors.affiliation: Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden.|Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, 200011 Shanghai, China.|Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, 200011 Shanghai, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, Key Laboratory and Unit of Infertility in Chinese Medicine, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, 150040 Harbin, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, Key Laboratory and Unit of Infertility in Chinese Medicine, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, 150040 Harbin, China.
authors.forename: Xiao-Ke
authors.initials: XK
authors.lastname: Wu
authors.affiliation: Department of Obstetrics and Gynecology, Sahlgrenska University Hospital at Sahlgrenska Academy, University of Gothenburg, 41345 Gothenburg, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Brännström
authors.affiliation: Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden.
authors.forename: Ruijin
authors.initials: R
authors.lastname: Shao
authors.affiliation: Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden.
authors.forename: Håkan
authors.initials: H
authors.lastname: Billig
mesh_terms: D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D005947:Glucose / Q000378:metabolism*; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D006019:Glycolysis / Q000235:genetics; D006801:Humans; D017588:Hyperandrogenism / Q000473:pathology*; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance / Q000235:genetics* / Q000502:physiology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D011085:Polycystic Ovary Syndrome / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014599:Uterus / Q000473:pathology
chemical_list: D006063:Chorionic Gonadotropin; D051246:Glucose Transport Proteins, Facilitative; D007328:Insulin; D019869:Phosphatidylinositol 3-Kinases; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D005947:Glucose