SPECIFIC EFFECTS OF ESTROGEN ON GROWTH-FACTOR AND MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II ANTIGEN EXPRESSION IN RAT AORTIC ALLOGRAFT

Objective: Transplant arteriosclerosis is the mdajor determinant for l ong-term survival of cardiac transplants, Estradiol treatment inhibits transplant arteriosclerosis. The objective of this study is to determ ine, in the absence of immunosuppression, the temporal effect of estra diol treatment on the expression of insulin-like growth factor, platel et-derived growth factor, basic fibroblast growth factor, and major hi stocompatibility complex class II antigen in rat aortic allografts, Me thods: Orthotopic abdominal aortic allograft transplantation was perfo rmed in male rats with Brown-Norway rats used as donors and Lewis rats as recipients, The recipients (n = 50) were treated,vith estradiol 20 mu g/kg per day or placebo by osmotic minipump for 2 days before the operation and until they mere put to death on postoperative days 1, 3, 7, 14, or 21, The allografts were harvested and insulin-like growth f actor, platelet-derived growth factor, basic fibroblast growth factor, and major histocompatibility complex class II antigen expression were determined by immunohistochemical staining, Myointimal thickening,vas measured by morphometric analysis, Results: In the placebo-treated gr oup, insulin-like growth factor protein progressively increased in all three layers of the allograft, whereas platelet-derived growth factor protein peaked at day 3 and basic fibroblast growth factor protein in creased only moderately, Estradiol treatment inhibited the continuous increase in insulin-like growth factor expression, the peak in platele t-derived growth factor expression at day 3, the moderate basic fibrob last growth factor increase at day 21, and major histocompatibility co mplex class II antigen expression in all three layers of the allograft at day 21, Intimal thickening of allografts from estradiol-treated re cipients was twofold to threefold less than that of the placebo-treate d recipients at day 21, Conclusion: The development of transplant arte riosclerosis is associated with an early alloimmune response involving sustained increase in insulin-like growth factor expression, Estradio l treatment of the recipient inhibits transplant arteriosclerosis and suppresses insulin-like growth factor and major histocompatibility com plex class II antigen expression but not platelet-derived growth facto r or basic fibroblast growth factor in all three layers of the allogra ft during the early posttransplantation alloimmune rejection phase.