Dean of the Medical Faculty, Semmelweis University
(PD-132851) Támogató: OTKA
(K-125174) Támogató: OTKA
(Fight for the Women’s Hearts Medical Foundation)
(Higher Education Institutional Excellence Programme of the Ministry of Human Capacities
in Hungary, within the framework of the molecular biology thematic program of the
Semmelweis University)
Szakterületek:
Orvos- és egészségtudomány
We examined the vasoactive effect of estradiol in a rat model of early PCOS and the
influence of vitamin D deficiency (VDD). We created a model of chronic hyperandrogenism
and VDD in adolescent female Wistar rats (N = 46) with four experimental groups: vitamin
D supplemented (T-D+), VDD (T-D-), hyperandrogenic and vitamin D supplemented (T+D+),
and hyperandrogenic and VDD (T+D-). T+ groups received an 8-week-long transdermal
Androgel treatment, D- animals were on vitamin D-reduced diet and D+ rats were supplemented
orally with vitamin D3. Estrogen-induced vasorelaxation of thoracic aorta segments
were measured with a wire myograph system with or without the inhibition of endothelial
nitric oxide synthase (eNOS) or cyclooxygenase-2 (COX-2). The distribution of estrogen
receptor (ER), eNOS and COX-2 in the aortic wall was assessed by immunohistochemistry.
VDD aortas showed significantly lower estradiol-induced relaxation independently of
androgenic status that was further decreased by COX-2 inhibition. COX-2 inhibition
failed to alter vessel function in D+ rats. Inhibition of eNOS abolished the estradiol-induced
relaxation in all groups. Changes in vascular function in VDD were accompanied by
significantly decreased ER and eNOS staining. Short-term chronic hyperandrogenism
failed to, but VDD induced vascular dysfunction, compromised estrogen-dependent vasodilatation
and changes in ER and eNOS immunostaining.
