GSK-3β mediates in the progesterone inhibition of estrogen induced cyclin D2 nuclear localization and cell proliferation in cyclin D1−/− mouse uterine epithelium

We report that glycogen synthase kinase (GSK)-3β is phosphorylated at ser9 and inactivated in uterine epithelial cells from E2-treated cyclin D1 null mutant mice. Simultaneous administration of P4 together with E2 blocked this effect. Pharmacological inhibition of GSK-3β activity in mice treated with P4E2 reversed the nuclear exclusion of cyclin D2 in the uterine epithelial cells and this caused phosphorylation of Rb protein and progression of cells towards S-phase. Our results indicate that GSK-3β is a major target of E2 and P4 in regulation of cyclin D2 localization in the mouse uterine epithelium.