Abstract
Cardiovascular diseases, the most common leading death diseases, occur more in men than women of the same ages. Increasing evidence shows that urocortin (Ucn1), an autocrine or paracrine pro-inflammatory factor, can be regulated by sex hormones. The purpose of the study is to investigate the role of Ucn1 in gender disparity in a sodium laurate-induced vasculitis model. Rats exhibited visible signs of vasculitis on the 14th day after sodium laurate injection. Inflammatory states of the rat femoral artery were observed by histological examination. Significant gender disparity, with the symptoms much grosser in males than females, was seen. In males, the serum levels of Ucn1, prostaglandin estradiol, and soluble intercellular adhesion molecule-1 and the expressions of Ucn1, cyclooxygenase-2, and intercellular adhesion molecule-1 in femoral artery were higher than those in females. Orchidectomy significantly ameliorated the symptoms of vasculitis accompanied with a decrease in the plasma Ucn1 level. However, estradiol supplement after orchidectomy failed to improve the inflammatory states further. In females, ovariectomy and/or dihydrotestosterone supplement significantly increased Ucn1 level and exacerbated symptoms of vasculitis. Furthermore, ip administration of rabbit antiserum to Ucn1 almost abolished the gender differences in vasculitis. These results demonstrated that vasculitis of this model is androgen-responsive and hormonal manipulation by surgical orchidectomy could substantially attenuate the symptoms of vasculitis. Moreover, Ucn1 is a contributory factor to the gender disparity in vasculitis and dihydrotestosterone-promoted Ucn1 secretion exacerbated the development of vasculitis.