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Title: Maximal Dexamethasone Inhibition of Luminal Epithelial Proliferation Involves Progesterone Receptor (PR)- and Non-PR-Mediated Mechanisms in Neonatal Mouse Uterus. Author: Nanjappa MK, Medrano TI, Lydon JP, Bigsby RM, Cooke PS. Journal: Biol Reprod; 2015 May; 92(5):122. PubMed ID: 25882702. Abstract: Progesterone (P4) and the synthetic glucocorticoid dexamethasone (Dex) inhibit luminal epithelial (LE) proliferation in neonatal mouse uteri. This study determined the roles of progesterone receptor and estrogen receptor 1 (PR and ESR1, respectively) in P4- and Dex-induced inhibition of LE proliferation using PR knockout (PRKO) and Esr1 knockout (Esr1KO) mice. Wild-type (WT), heterozygous, and homozygous PRKO female pups were injected with vehicle, P4 (40 μg/g body weight), or Dex (4 or 40 μg/g body weight) on Postnatal Day 5, then 24 h later immunostained for markers of cell proliferation. In WT and heterozygous mice, P4 sharply reduced LE proliferation, and Dex produced dose-responsive decreases equaling those of P4 at the higher dose. Critically, although both doses of Dex similarly decreased proliferation compared to vehicle-treated PRKOs, treatment of PRKO pups with the high Dex dose (40 μg/g) did not inhibit LE as much as treatments of WT mice with this Dex dose or with P4. Stromal proliferation was stimulated by P4 in WT but not PRKO mice, and Dex did not alter stromal proliferation. Uteri of all genotypes strongly expressed glucocorticoid receptor (GR), demonstrating that impaired Dex effects in PRKOs did not reflect GR deficiency. Furthermore, inhibition of LE proliferation by Dex (40 μg/g body weight) in Esr1KO mice was normal, so this process does not involve ESR1. In summary, inhibitory Dex effects on LE proliferation occur partially through non-PR-mediated mechanisms, presumably GR, as indicated by Dex inhibition of LE proliferation in PRKOs. However, maximal inhibitory Dex effects on uterine LE proliferation are not seen in PRKO mice with even high Dex, indicating that maximal Dex effects in WT mice also involve PR.[Abstract] [Full Text] [Related] [New Search]