title: Reproductive and metabolic phenotype of a mouse model of PCOS.
abstract: Polycystic ovary syndrome (PCOS), the most common endocrine disorder in women in their reproductive age, is characterized by both reproductive and metabolic features. Recent studies in human, nonhuman primates, and sheep suggest that hyperandrogenism plays an important role in the development of PCOS. We investigated whether chronic dihydrotestosterone (DHT) exposure in mice reproduces both features of PCOS. Such a model would allow us to study the mechanism of association between the reproductive and metabolic features in transgenic mice. In this study, prepubertal female mice received a 90 d continuous release pellet containing the nonaromatizable androgen DHT or vehicle. At the end of the treatment period, DHT-treated mice were in continuous anestrous, their ovaries contained an increased number of atretic follicles, with the majority of atretic antral follicles having a cyst-like structure. Chronic DHT-exposed mice had significantly higher body weights (21%) than vehicle-treated mice. In addition, fat depots of DHT-treated mice displayed an increased number of enlarged adipocytes (P < 0.003). Leptin levels were elevated (P < 0.013), adiponectin levels were diminished (P < 0.001), and DHT-treated mice were glucose intolerant (P < 0.001). In conclusion, a mouse model of PCOS has been developed showing reproductive and metabolic characteristics associated with PCOS in women.
authors.affiliation: Department of Internal Medicine, Erasmus MC, 3000 CA Rotterdam, The Netherlands.
authors.forename: E Leonie A F
authors.initials: EL
authors.lastname: van Houten
authors.forename: Piet
authors.initials: P
authors.lastname: Kramer
authors.forename: Anke
authors.initials: A
authors.lastname: McLuskey
authors.forename: Bas
authors.initials: B
authors.lastname: Karels
authors.forename: Axel P N
authors.initials: AP
authors.lastname: Themmen
authors.forename: Jenny A
authors.initials: JA
authors.lastname: Visser
mesh_terms: D052242:Adiponectin / Q000097:blood; D000818:Animals; D001835:Body Weight / Q000502:physiology; D013196:Dihydrotestosterone; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D050356:Lipid Metabolism / Q000502:physiology*; D007986:Luteinizing Hormone / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D006080:Ovarian Follicle / Q000378:metabolism / Q000473:pathology; D010053:Ovary / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D011085:Polycystic Ovary Syndrome / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology*; D012098:Reproduction / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D052242:Adiponectin; D007328:Insulin; D020738:Leptin; D013196:Dihydrotestosterone; D007986:Luteinizing Hormone