title: Analysis of the vascular responses in a murine model of polycystic ovary syndrome.
abstract: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of there productive age, but the exact pathophysiological mechanisms involved remain unclear. Cardiovascular disease risk is increased in PCOS patients and endothelial damage has been observed. We recently developed a mouse model of PCOS with reproductive and metabolic characteristics resembling those observed in women with PCOS. In this model we studied vascular function with particular emphasis on markers of vascular endothelial function. Animals were treated for 90 days with dihydrotestosterone (DHT; 27.5 mg/day) or placebo using subcutaneous continuous-release pellets. Aortas were isolated for isometric force recordings in organ baths to investigate endothelial and vascular smooth muscle characteristics. Lungs were used to analyze endothelial nitric oxide synthase (eNOS) expression and phosphorylation. Asymmetric dimethylarginine (ADMA) levels were investigated in serum to assess endothelial damage. Expression of androgen receptor (Ar) mRNA was studied in aortas. DHT treatment (compared with placebo) induced i) a significant decrease in acetylcholine-induced aortic relaxations, with no change in calcitonin gene related peptide- or sodium nitroprusside-induced relaxations, as well as 5-hydroxytryptamine-induced contractions; ii) no change in eNOS expression/phosphorylation in lungs or in plasma ADMA levels; and iii) a twofold increase in aortic AR expression. Our results suggest that, in DHT-exposed mice, hyperandrogenemia specifically decreases endothelium dependent vasorelaxation without deterioration of smooth muscle function. This study may initiate further investigations to elucidate underlying mechanism for the phenotype that is present in these animals, as well as in PCOS patients.
authors.affiliation: Division of Vascular Medicine and Pharmacology, Erasmus MC, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Sieneke
authors.initials: S
authors.lastname: Labruijere
authors.forename: E Leonie A F
authors.initials: EL
authors.lastname: van Houten
authors.forename: René
authors.initials: R
authors.lastname: de Vries
authors.forename: Usha M
authors.initials: UM
authors.lastname: Musterd-Bagghoe
authors.forename: Ingrid M
authors.initials: IM
authors.lastname: Garrelds
authors.forename: Piet
authors.initials: P
authors.lastname: Kramer
authors.forename: A H Jan
authors.initials: AH
authors.lastname: Danser
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Villalón
authors.forename: Jenny A
authors.initials: JA
authors.lastname: Visser
authors.forename: Antoinette Maassen
authors.initials: AM
authors.lastname: Van Den Brink
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000503:physiopathology*; D013196:Dihydrotestosterone / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D011085:Polycystic Ovary Syndrome / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology*; D014664:Vasodilation
chemical_list: D013196:Dihydrotestosterone; D000109:Acetylcholine