PROGESTERONE AND ESTROGEN-RECEPTORS IN THE DECIDUALIZED MOUSE UTERUS AND EFFECTS OF DIFFERENT TYPES OF ANTIPROGESTERONE TREATMENT

Pseudopregnant mice were treated systemically with monoclonal anti-pro gesterone antibody (DB3) (model I), or progesterone receptor antagonis ts RU486 or ZK98,299 (ZK299) (model 2) on day 3 post coitum. On day 4, sesame oil was administered intraluminally into one uterine horn to i nduce decidualization. On day 7, the average mass of the oil-injected horn was 335.2+/-52.4 mg, eight times greater than that of the non-inj ected horn (40.8 +/- 5.3 mg; P < 0.001). After treatment with DB3, RU4 86 or ZK299, the masses of the injected hems did not differ significan tly from those of non-injected horns. In the control group, concentrat ions of progesterone receptors (ligand-binding assay) increased twofol d in the decidualized (52.2+/-7.4 fmol mg(-1)) compared with the non-i njected horn (26.0 +/- 7.6 fmol mg(-1); P < 0.05), whereas oestrogen r eceptor content (ligand-exchange assay) decreased by 53% (104.9 +/- 18 .2 versus 224.3 +/- 18.1 fmol mg(-1); P< 0.001). In model I, antibody- treated animals showed a tenfold increase in the concentration of prog esterone receptors (261.7 +/- 81.1 fmol mg (-1); P < 0.001), but there was no differential distribution of progesterone or oestrogen recepto rs in the oil-injected versus non-injected uterine horns. In model 2, uterine progesterone and oestrogen receptors again showed no different ial response between injected and non-injected hems regardless of the route of administration (systemic or intraluminal). Concentrations of progesterone receptors in RU486-treated (35.8 +/- 9.4 fmol mg(-1)) and ZK299-treated (32.0 +/- 10.2 fmol mg(-1)) mice were comparable to tho se in non-injected hems (35.3 +/- 6.3 and 34.2 +/- 5.1 fmol mg(-1) res pectively) and were not significantly different from the control group (26.0 +/- 7.6 fmol mg(-1)). The results show that oil-induced decidua lization is accompanied by increased concentrations of progesterone re ceptors and decreased concentrations of oestrogen receptors. When deci dualization is blocked by anti-progesterone treatment (antibody agains t progesterone or progesterone receptor antagonist), there are differi ng effects on receptor responses with an increase in progesterone rece ptors and decrease in oestrogen receptors after passive immunization, and no change in progesterone receptors and a reduction in oestrogen r eceptors after anti-progestins. The anti-decidualization effect in the two models was therefore achieved via dissimilar uterine receptor res ponses.