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.

用雌二醇-17β（E_2）（8mg/kg体重）对C57BL/6雄性小鼠进行新生治疗，从出生之日起连续治疗5次（E_2-0），诱导前列腺上皮增生和/或异型增生。当在出生后第 7 天（E_2-7）开始治疗时，所有小鼠均出现类似的上皮异常，但炎症的影响较小。当第 14 天开始注射 E_2 (E_2-14) 时，大约有一半的小鼠出现了细胞浸润。在第 3 天的胸腺切除术 (Tx) 后，约 35% 的 C57BL/6 小鼠自发出现了自身免疫性前列腺炎。 (Tx-3) 当 Tx-3 小鼠从第 7 天 (Tx-3 + E_2-7) 或第 7 天接受 E_2 注射时。第 14 天（Tx-3 + E_2-14）但不是第 21 天（Tx-3 + E_2-21），严重前列腺炎的发生率很高（约 80%），即使注射丙酸睾酮 (TP) 也没有效果。在患有前列腺炎的 Tx-3 小鼠的血清中检测到了针对前列腺上皮细胞的自身抗体，无论是否注射了 E_2，但从未检测到。将新生前列腺移植到患有前列腺炎的 Tx-3 或 Tx-3 + E_2-14 小鼠的肾囊下会引起移植物周围的强烈炎症，而移植到 E_2-0 小鼠中从未出现过这种炎症反应。腹膜内注射正常脾细胞可以预防 Tx-3 和 Tx-3 + E_2-14 小鼠前列腺炎的发生，但不能预防 E_2-0 小鼠的前列腺炎。第 7 天的雄性小鼠。我们得出结论，效应细胞属于 CD4^+CD25^+ 类淋巴细胞。