PROMOTING EFFECTS OF JUVENILE ESTROGEN TREATMENT ON DEVELOPMENT OF AUTOIMMUNE PROSTATITIS IN NEONATALLY THYMECTOMIZED MICE

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Neonatal treatment of C57BL/6 male mice with estradiol-17β (E_2) (8mg/kg body weight) induces prostate epithelial hyperplasia and/or dysplasia with inflammatory cell infiltration. Five-consecutive-treatment from the day of birth (E_2-0)induced lesions in all mice. When the treatment was started on day 7 after birth (E_2-7), similar epithelial abnormalities with a lesser exert of inflammatory cell infiltration were caused in about the half mice. Few prostatic lesions were found when E_2 injection was started on day 14 (E_2- 14). Autoimmune prostatitis developed spontaneously in approximately 35% of C57BL/6 mice after thymectomy (Tx) on day 3 (Tx-3) after birth. When Tx-3 mice received E_2 injections from day 7 (Tx-3 + E_2-7) or day 14 (Tx-3 + E_2-14) but not day 21 (Tx-3 + E_2-21), a high incidence (around 80%) of severe prostatitis developed. Injections of testosterone propionate (TP) were without effect, even when given at young age. Autoantibodies against prostate epithelial cells were detected in the sera of Tx-3 mice with prostatitis, irrespective of whether given E_2 injections but never neonatal E_2 exposure alone. Transplantation of newborn prostate under the kidney capsules of Tx-3 or Tx-3 + E_2-14 mice with prostatitis evoked intense inflammation around the grafts. Such an inflammatory reaction was never seen with transplants into the E_2-0 mice. Development of prostatitis in Tx-3 and Tx-3 + E_2-14 but not E_2-0 mice could be prevented by the intraperitoneal injection of spleen cells from normal male mice at day 7. We conclude that effector belongs to the CD4^+CD25^+ class of lymphocytes.