title: Selective impairment in glycogen synthase kinase-3 and mitogen-activated protein kinase phosphorylation: comparisons with the hyperandrogenic and the hyperinsulinemic rats.
abstract: OBJECTIVE
  To characterize and compare the effect of DHEA and insulin plus hCG on ovarian morphology, estrous cycle, hormonal levels, insulin sensitivity, and the regulation of insulin signaling in rats.
  
  
  METHODS
  Animal model study.
  
  
  METHODS
  University laboratory.
  
  
  METHODS
  Female Sprague-Dawley rats.
  
  
  METHODS
  Female rats received DHEA or insulin plus hCG by continuous administration.
  
  
  METHODS
  Ovarian morphology, estrous cycle, hormonal levels, insulin sensitivity, protein levels, and phosphorylation state of glycogen synthase kinase-3beta and extracellular regulated kinase 1/2 in the ovary.
  
  
  RESULTS
  Rats treated with DHEA displayed anovulation, insulin resistance, and polycystic ovaries characterized by cysts and a diminished granulosa layer. In contrast, insulin plus hCG results in acyclicity with increasing androgen biosynthesis and ovarian morphology different from that in DHEA-treated rats. Moreover, we found that insulin-stimulated serine-phosphorylation of glycogen synthase kinase-3beta was higher in insulin plus hCG-treated rats but lower in DHEA-treated rats. Furthermore, basal and insulin-stimulated tyrosine-phosphorylation of extracellular regulated kinase 1/2 was higher in DHEA-treated rats than in controls.
  
  
  CONCLUSIONS
  Notwithstanding that both the hyperandrogenism and the hyperinsulinemia synergistic with hCG-treated rats displayed the typical traits of human polycystic ovary syndrome, there is a divergence in the insulin-signaling pathway in the ovarian tissue, which may have a role in the pathogenesis of polycystic ovary syndrome.
authors.affiliation: Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, People's Republic of China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, People's Republic of China. Electronic address: jie.qiao@263.net.
authors.forename: Jie
authors.initials: J
authors.lastname: Qiao
authors.affiliation: Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, People's Republic of China.
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Yan
authors.affiliation: Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, People's Republic of China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Huang
authors.affiliation: Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, People's Republic of China.
authors.forename: Pan-Lin
authors.initials: PL
authors.lastname: Zhao
authors.affiliation: Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yan
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D006063:Chorionic Gonadotropin / Q000008:administration & dosage / Q000494:pharmacology; D003687:Dehydroepiandrosterone / Q000494:pharmacology; D030762:Estrous Cycle / Q000187:drug effects / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D005951:Glucose Tolerance Test; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D017588:Hyperandrogenism / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D006946:Hyperinsulinism / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D007328:Insulin / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D010053:Ovary / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013379:Substrate Specificity
chemical_list: D001786:Blood Glucose; D006063:Chorionic Gonadotropin; D007328:Insulin; D003687:Dehydroepiandrosterone; D048049:Extracellular Signal-Regulated MAP Kinases; D038362:Glycogen Synthase Kinase 3