In polycystic ovary syndrome (PCO), the metabolic and cardiovascular dysfunction is related to the hyperandrogenic status and insulin resistance (IR). Vitamin D3 is beneficial in insulin resistance partly due to its anti-oxidant effect. Vitamin D3 has positive impact on the symptoms of PCO, however the cause and effect relations are still unknown. It is also known that women with PCO have lower D3 levels. Nitrative stress is a major factor in the development of cardiovascular dysfunction and IR in various diseases. Our aim was to determine the effects of vitamin D3 on the glucose metabolism and vascular function in a rat model of PCO, particulary the pathogenetic role of nitrative stress. Female Wistar rats weighing 100–140 g were administered vehicle (C; n=10), dihydrotestosterone (T:7.5mg/kg/week, sc. pellet; n=10), or dihydrotestosterone plus vitamin D3 (T+D; D3:1.2mg/kg/week, sc.; n=10). Oral glucose tolerance test (OGTT) was performed 8 weeks following treatment. On the 10th week insulin and acetyl-choline (Ach) induced relaxation ability of the isolated thoracic aortae was measured as the percent of norepinephrine precontraction. Circulating leukocyte smears and paraffin embedded sections of aortae and ovaries were immunostained with polyclona anti-nitrotyrosine rabbit antibody to determine nitrative stress (staining intensity was scored between 1–10 by a blinded experimenter). For data analysis ANOVA and Tukey's post hoc test were implemented. In the 120th minute of OGTT, insulin response (insulin/glucose) was significantly elevated in group T, which was reduced by vitamin D3 (C: 93.3±15.1; T: 232.4±57; T+D: 57.5±2.7 mg/mol; mean±SEM, p<=0.05 T vs. C and T+D). Also, the relaxation ability of aortae was hampered in group T, and Vitamin D3 increased only the Ach induced relaxation (Ach 0.000001M: C: 78.9±2%; T: 38.1±4%; T+D: 54±3.5%; p<=0,001 T vs. C and. T+D). Nitrative stress in circulating leukocytes, aortae and ovaries showed a significant increase as a response to dihydrotestosterone and vitamin D3 treatmentreversed this effect in case of the ovaries (C: 2.3±0.3; T: 4.2±0.6; T+D: 2.9±0.3; p<=0.05 T vs. C).

According to our results, treatment with vitamin D3 reduces insulin resistance, endothelial dysfunction and nitrative stress in a rat model of PCO. Based on this study, nitrative stress may have a role in the pathogenesis of PCO and the therapeutic effect of vitamin D3.