Estradiol enhances murine cardiac allograft rejection under cyclosporin and can be antagonized by the antiestrogen tamoxifen

Background. An increased incidence of acute rejection episodes in female heart transplant recipients has been reported in experimental and clinical studies. However, the exact mechanisms of gender-specific differences in alloreactivity are not completely understood. Methods. C57BL/10 (H-2b) hearts were transplanted into C3H/He (H-2 k) recipients. Four gender combinations were used to test the influence of donor and recipient sex on graft survival. Recipients were treated with CsA, 17β-estradiol and/or tamoxifen. Additionally mice were ovariectomized prior to transplantation. Results. Treated with CsA, allograft survival in female recipients was 9.16±0.41 days as compared with 15.16±1.72 days in males. Estradiol administration and oophorectomy had a significant impact on allograft survival in male and female mice under CsA treatment. Tamoxifen combined with CsA significantly prolonged graft survival in female recipients (13.16±1.16 days) as compared with CsA treatment alone (9.16±0.41 days). Conclusion. Female mice show earlier rejection episodes and a shorter graft survival than males. For the first time, tamoxifen has been shown to have a beneficial effect on heart allograft survival in female recipients.