Effects of sex steroid hormones on sex-associated differences in the survival time of allogeneic skin grafts in rats. Evidence that testosterone enhances and estradiol reverses the immunosuppressive activity of cyclosporine.

ABSTRACT

Three-week-old DA (RT1a) male and female rats were pretreated with either orchiectomy or ovariectomy and administration of the opposite-sex steroid hormones, estradiol or testosterone. Skin from same-sex AO (RT1a) rats was then grafted when these pretreated rats reached 14 weeks of age, with a short course of immunosuppressive treatment of cyclosporine. The survival times of the grafts were reversed in that the male recipients pretreated to be like females acutely rejected the graft within 10 days as do normal adult female recipients. On the other hand, the female recipients pretreated to be like males accepted the graft as do normal adult male recipients. In addition, the synergistic effects of either testosterone or estradiol with CsA on the survival time of the graft were examined. Testosterone successfully prolonged graft survival on normal adult female and young male recipients, but negligible prolongation was observed on young females. In contrast, estradiol abrogated the immunosuppressive activity of CsA and accelerated graft rejection in both male and female recipients.