Proto-oncogene erbA expression and increased abundance of progesterone receptors in the mouse uterus after passive immunisation against progesterone before implantation.

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.