Disruption of estrogen signaling does not prevent progesterone action in the estrogen receptor or knockout mouse uterus

Estrogen is known to increase progesterone receptor (PR) levels in the wild -type mouse uterus, and this estrogen induction was thought to he important for progesterone action through the PR. The estrogen receptor alpha knocko ut (ERKO) mouse uterus was observed to express PR mRNA that cannot be induc ed by estrogen, Progesterone action mas characterized to determine whether it was diminished in ERKO mice. The PR protein is present in the ERKO uteru s at 60% of the level measured in a wild-type uterus, The PR-A and PR-B iso forms are both detected on Western blot, and the ratio of isoforms is the s ame in both genotypes, Although the level of PR is reduced in the ERKO uter us, the receptor level is sufficient to induce genomic responses, since bot h calcitonin and amphiregulin mRNAs were increased after progesterone treat ment. Finally, the ERKO uterus can be induced to undergo a progesterone-dep endent decidual response, Surprisingly, the decidual response is estrogen i ndependent in the ERKO, although it remains estrogen dependent in a wild ty pe, These results indicate that estrogen receptor alpha modulation of PR le vels is not necessary for expression of the PR or genomic and physiologic r esponses to progesterone in the ERKO uterus.