Whyte A, Wang M W, Cheng J T, Heap R B
Department of Immunology, AFRC Institute of Animal Physiology and Genetics Research, Babraham, Cambridge, UK.
J Reprod Immunol. 1992 Aug;22(2):153-72. doi: 10.1016/0165-0378(92)90013-t.
Passive immunisation with a monoclonal anti-progesterone antibody (DB3) prevents pregnancy in the mouse, and antibody is localised in the endometrium before the onset of implantation. BALB/c female mice were injected intraperitoneally with 9 nmol of DB3 (a dose known to cause 100% infertility) 32 h post coitum, and the uterus was removed at various times after injection. Using a monoclonal anti-progesterone receptor antibody (PR6), expression of progesterone receptors was found to be abundant in uterine tissue of DB3-treated mice; this was associated with substantial progesterone receptor mRNA levels and with maximum localisation of DB3 antibody as detected by anti-idiotype antibody. Control animals treated with an equal amount of the mouse myeloma protein P3 showed very low levels of progesterone receptor in the uterus. DB3 treatment also affected uterine expression of the proto-oncogene erbA product (which shows primary sequence homology with the progesterone receptor) as revealed by specific antiserum to the ERBA protein and by in situ hybridisation with a cDNA probe to v-erbA. Time-course studies indicated that the erbA gene was expressed at a high level before progesterone receptor expression increased, that its expression was dependent on the presence of the embryo and that erbA expression persisted longer in DB3-treated females. The observations suggest that anti-progesterone immunisation has a direct effect within the uterus, involving persistence of proto-oncogene erbA expression (which itself may represent an early maternal response to pregnancy) and increased progesterone receptor levels resulting from an unopposed oestrogen effect derived from local ligand withdrawal.
用单克隆抗孕酮抗体（DB3）进行被动免疫可防止小鼠怀孕，且抗体在着床开始前定位于子宫内膜。在交配后32小时，给BALB/c雌性小鼠腹腔注射9 nmol的DB3（已知该剂量可导致100%不孕），并在注射后的不同时间取出子宫。使用单克隆抗孕酮受体抗体（PR6），发现DB3处理的小鼠子宫组织中孕酮受体表达丰富；这与大量的孕酮受体mRNA水平以及抗独特型抗体检测到的DB3抗体最大定位有关。用等量小鼠骨髓瘤蛋白P3处理的对照动物子宫中孕酮受体水平非常低。DB3处理还影响原癌基因erbA产物（其与孕酮受体具有一级序列同源性）的子宫表达，这通过针对ERBA蛋白的特异性抗血清以及与v-erbA的cDNA探针进行原位杂交得以揭示。时间进程研究表明，erbA基因在孕酮受体表达增加之前高水平表达，其表达依赖于胚胎的存在，并且erbA表达在DB3处理的雌性小鼠中持续时间更长。这些观察结果表明，抗孕酮免疫在子宫内具有直接作用，涉及原癌基因erbA表达的持续存在（其本身可能代表母体对怀孕的早期反应）以及由于局部配体撤离导致的雌激素作用未受对抗而引起的孕酮受体水平增加。
