Progesterone and oestrogen receptors in the decidualized mouse uterus and effects of different types of anti-progesterone treatment.
Pseudopregnant mice were treated systemically with monoclonal anti-progesterone antibody (DB3) (model 1), or progesterone receptor antagonists 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 induce 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-injected horn (40.8 +/- 5.3 mg; P < 0.001). After treatment with DB3, RU486 or ZK299, the masses of the injected horns did not differ significantly from those of non-injected horns. In the control group, concentrations of progesterone receptors (ligand-binding assay) increased twofold in the decidualized (52.2 +/- 7.4 fmol mg-1) compared with the non-injected horn (26.0 +/- 7.6 fmol mg-1; P < 0.05), whereas oestrogen receptor content (ligand-exchange assay) decreased by 53% (104.9 +/- 18.2 versus 224.3 +/- 18.1 fmol mg-1; P < 0.001). In model 1, antibody-treated animals showed a tenfold increase in the concentration of progesterone receptors (261.7 +/- 81.1 fmol mg-1; P < 0.001), but there was no differential distribution of progesterone or oestrogen receptors in the oil-injected versus non-injected uterine horns. In model 2, uterine progesterone and oestrogen receptors again showed no differential response between injected and non-injected horns 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 those in non-injected horns (35.3 +/- 6.3 and 34.2 +/- 5.1 fmol mg-1, respectively) and were not significantly different from the control group (26.0 +/- 7.6 fmol mg-1). The results show that oil-induced decidualization is accompanied by increased concentrations of progesterone receptors and decreased concentrations of oestrogen receptors. When decidualization is blocked by anti-progesterone treatment (antibody against progesterone or progesterone receptor antagonist), there are differing effects on receptor responses with an increase in progesterone receptors and decrease in oestrogen receptors after passive immunization, and no change in progesterone receptors and a reduction in oestrogen receptors after anti-progestins. The anti-decidualization effect in the two models was therefore achieved via dissimilar uterine receptor responses.
Parandoosh
Z
Z
Ligand Pharmaceuticals, Inc., San Diego, CA 92121, USA.
Crombie
D L
DL
Tetzke
T A
TA
Hayes
J S
JS
Heap
R B
RB
Wang
M W
MW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D003656:Decidua / Q000187:drug effects / Q000254:growth & development*; D005260:Female; D006067:Gonanes / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D015735:Mifepristone / Q000494:pharmacology; D011374:Progesterone / Q000037:antagonists & inhibitors / Q000276:immunology; D011555:Pseudopregnancy / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000187:drug effects*; D011980:Receptors, Progesterone / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D006067:Gonanes; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D015735:Mifepristone; D011374:Progesterone; C053238:onapristone