In polycystic ovary syndrome (PCOS) significant changes in pharmacological reactivity develop parallel with histological damage of large blood vessels, and these alterations are related to insulin resistance. The decline of vasomotor effects of estrogen is mainly due to hyperandrogen status. Vitamin D reduces the symptoms of PCO and also, together with estrogen, a known endogenous PARP inhibitor.

The aim of our study were

- to detect the vasodilatory effect of estrogen on rat aorta rings in hyperandrogenic milieu,

- to measure poly(ADP-ribose) polymerase 1 (PARP) activation in ovary, aorta and circulating leukocytes,

- to specify the effects of therapeutic dose of Vitamin D on the above mentioned parameters in a rat model of PCOS.

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 - vitamin D combined dosage (T+D; D3:1.2mg/kg/week, sc.; n=10). On the 10th week estrogen-induced relaxation ability of the isolated thoracic aortae was determined after norepinephrine precontraction. Circulating leukocyte smears and paraffin-embedded sections of aortae and ovaries were immunostained with anti-poly(ADP-ribose) antibody (staining intensity was scored between 1–10 by a blinded experimenter).

Estrogen in physiological dose (10^­5–10^­4M) exerted limited relaxation in DHT-administered groups compared to controls (10^­5 M: T:21±3% and T+D: 20±3% vs. C:42±5%, p<=0.05). Immunohistochemical analysis showed that the most pronounced PARP activity was found in the ovaries (T:8.4±1.1 vs. C: 3.8±1 p<=0.001 and D:4.7±0.9 p<=0.01) and leukocytes (T:6.5±1.2 vs. C: 6.1±0.6 p<=0.001 and D:7.5±0.9 p<=0.05) of T animals, while Vitamin D treatment significantly reduced this activation in the ovaries. On the other hand DHT treatment significantly reduced the PARP activity both in the endothelial and smooth muscle layers of the aortae and Vitamin D treatment did not alter this effect (smooth muscle: C:4.9±1.9 vs. T: 2.1±1 p<=0.001 and D:3.0±0.8 p<=0.001; endothel: C:5.5±1.8 vs. T: 3.0±1.3 p<=0.001 and D:3.8±1.3 p<=0.01).

According to our results hyperandrogenic status and Vitamin D exert controversial effects on poly(ADP-ribosyl)ation. Although ovaries in T group showed polycystic physiognomy that was reversed by Vitamin D, in the arteries dihydrotestosterone inhibited poly(ADP-ribosyl)ation but damaged endothelium-dependent relaxation. Additionally, Vitamin D did not affect estrogen-induced vasodilation.