Sex hormones and gender-related differences: Their influence on chronic renal allograft rejection

Background. Renal hemodynamics and immune responses differ between males an d females. Thus, sex hormones and genetically determined gender differences may determine the process of chronic rejection to some extent. Methods. Female (F) or male (M) F344 kidneys were orthotopically transplant ed into ovariectomized female Lewis recipients and were treated for 16 week s with either estradiol, testosterone, or vehicle. Results. Testosterone treatment resulted in increased urinary protein excre tion independently of the donor gender, as well as extended glomerular scle rosis, interstitial fibrosis, and severe vascular lesions. Additionally, mo nonuclear cell infiltration was most pronounced in these animals, in parall el to an increased expression of intercellular adhesion molecule-1 (ICAM-1) , fibronectin, laminin, and transforming growth factor-beta (TGF-beta) in t he grafts. Estradiol treatment resulted in an improved graft function, redu ced glomerular sclerosis, and a diminished cellular infiltration, in parall el to a reduced ICAM-1, fibronectin, laminin, and TGF-beta expression. In a nimals treated with vehicle, the gender of the donor influenced the outcome . Grafts of male origin had good graft function and histology, whereas graf ts from female donors developed severe proteinuria and glomerular, intersti tial, and vascular damage. Conclusions. These results suggest that a protective effect of estradiol on the progression of chronic rejection exists that is independent of donor g ender. Additionally, a male kidney may benefit from the absence of testoste rone, whereas the function of a female kidney deteriorates in the absence o f estradiol.