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

幼年雌激素治疗对新生胸腺切除小鼠自身免疫性前列腺炎发展的促进作用

基本信息

批准号：
13671684
负责人：
HAYASHI Norio
金额：
$ 2.05万
依托单位：
AICHI CANCER CENTER RESEARCH INSTITUTE
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671684/
关键词：
ESTROGEN PROSTATE MOUSE THYMECTOMY PROSTATITIS AUTO IMMUNE NEONATAL

项目摘要

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.

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。