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

雌二醇-17β (E_2) （8mg/kg体重）对新生C57BL/6雄性小鼠可诱导前列腺上皮增生和/或异常增生伴炎症细胞浸润。从出生之日起（E_2-0）连续5次给药，所有小鼠均出现病变。当在出生后第7天（E_2-7）开始治疗时，大约一半的小鼠出现了类似的上皮异常，但炎症细胞浸润的作用较小。第14天开始注射E_2 (E_2- 14)，前列腺病变极少。在出生后第3天（Tx-3）胸腺切除术（Tx）后，约35%的C57BL/6小鼠自发发生自身免疫性前列腺炎。当Tx-3小鼠从第7天（Tx-3 + E_2-7）或第14天（Tx-3 + E_2-14）而不是第21天（Tx-3 + E_2-21）注射E_2时，发生严重前列腺炎的发生率很高（约80%）。注射丙酸睾酮（TP）没有效果，即使在年轻时给予。在前列腺炎的Tx-3小鼠血清中检测到针对前列腺上皮细胞的自身抗体，无论是否注射E_2，但新生儿单独暴露E_2从未检测到。新生前列腺移植于患有前列腺炎的Tx-3或Tx-3 + E_2-14小鼠肾胶囊下，可引起移植物周围强烈的炎症反应。这种炎症反应在E_2-0小鼠移植中从未出现过。腹腔注射正常雄鼠脾细胞可防止Tx-3和Tx-3 + E_2-14小鼠前列腺炎的发生，但对E_2-0小鼠无抑制作用。我们得出结论，效应物属于CD4^+CD25^+类淋巴细胞。

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.