ESTROGEN INDUCES EARLY AND TIMED ACTIVATION OF CYCLIN-DEPENDENT KINASE-4, KINASE-5, AND KINASE-6 AND INCREASES CYCLIN MESSENGER-RIBONUCLEIC-ACID EXPRESSION IN RAT UTERUS

Cyclin-dependent kinases (cdks) are serine-threonine protein kinases t hat play a key role in the regulation of the mitotic cycle, in transcr iption initiation, and in the control of specific metabolic path ways in eukaryotic cells, cdh activity is controlled via phosphode-phosphor ylation of the catalytic subunits of these enzymes and their physical association with cyclins and cdh inhibitors. In adult rats, estrogen s timulation results in massive proliferation of endometrial epithelial cells, accompanied by functional and structural modifications in all o ther tissue components of the uterus. We report here that administrati on of 17 beta-estradiol (E(2)) to adult ovariectomized rats induces wi thin the first 25 h significant activation of cdk 4, 5, and 6, but not cdk 2, in the uterus, accompanied by increased expression of D-type ( D1-3), A and E cyclin messenger RNAs (mRNAs). Furthermore, Expression of the cdk inhibitor p27(Kip1), a key regulator of uterine functions, is induced by E(2) in this organ. Analysis of RNA extracted from E(2)- stimulated rat endometria shows early accumulation of D1 and D3, but n ot D2, cyclin mRNA, preceded by transient accumulation of c-fos mRNA. These results indicate an involvement of cdks and cyclins in estrogen actions in adult rat uterus and suggest that cyclins D1 and D3 are par t of the molecular pathway that allows hormonal regulation of G(1) pro gression in endometrial cells.