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

新生C57BL/6雄性小鼠经17雌二醇(Edidiol-17β，E_2)(8 mg/kg体重)处理后，可引起前列腺上皮细胞增生和/或异型增生，并伴有炎性细胞浸润。从出生之日起连续5次给药(E_2-0)可引起所有小鼠的损伤。在出生后第7天(E_2-7)开始治疗时，大约一半的小鼠出现类似的上皮异常，炎性细胞浸润较少。E_2注射后第14天(E_2~14天)可见少量前列腺病变。在出生后第3天(TX-3)，约有35%的C57BL/6小鼠在胸腺切除(TX)后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)开始注射E_2而不是第21天(TX-3+E_2-21)注射E_2时，严重前列腺炎的发生率高(约80%)。注射丙酸睾丸酮(TP)没有效果，即使在很小的时候也是如此。在TX-3前列腺炎小鼠血清中检测到抗前列腺上皮细胞自身抗体，无论是否注射E_2，但从未单独给予新生E_2暴露。TX-3或TX-3+E_2-14前列腺炎小鼠肾包膜下移植新生前列腺可引起移植物周围强烈的炎症反应。这种炎症反应在移植到E_2-0小鼠身上从未见过。TX-3和TX-3+E_2-14小鼠在第7天经腹腔注射正常雄性小鼠的脾细胞，可阻止前列腺炎的发生，但对E_2-0小鼠的前列腺炎无影响。

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.