Influence of Vitamin D on the Vasoactive Effect of Estradiol in a Rat Model of Polycystic Ovary Syndrome

• Published in: International journal of molecular sciences Vol. 22; no. 17; p. 9404
• Main Authors: Tarszabó, Róbert, Bányai, Bálint, Ruisanchez, Éva, Péterffy, Borbála, Korsós-Novák, Ágnes, Lajtai, Krisztina, Sziva, Réka Eszter, Gerszi, Dóra, Hosszú, Ádám, Benkő, Rita, Benyó, Zoltán, Horváth, Eszter Mária, Masszi, Gabriella, Várbíró, Szabolcs
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.09.2021; MDPI
• Subjects: 17β-Estradiol; Animal models; Animals; Aorta; Calciferol; Chronic illnesses; Coronary vessels; Cyclooxygenase-2; Disease; Enzymes; estradiol relaxation; Estrogen receptors; Estrogens; Hypertension; Immunohistochemistry; Influence; Insulin resistance; Kinases; Metabolism; Metabolites; Morphology; Nitric oxide; Nitric-oxide synthase; Nutrient deficiency; Ovaries; Polycystic ovary syndrome; rat model; Sex hormones; Testosterone; testosterone treatment; Thorax; Vasoactive agents; Vasodilation; Vitamin D; vitamin D deficiency; Vitamin D3; Vitamin deficiency; Womens health
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22179404

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.