Mol. Hum. Reprod. Advance Access originally published online on August 1, 2006
Molecular Human Reproduction 2006 12(9):543-549; doi:10.1093/molehr/gal065
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Expression of endometrial glycogen synthase kinase-3ß protein throughout the menstrual cycle and its regulation by progesterone
1Department of Internal Medicine, 2Department of Obstetrics and Gynecology and 3Department of Pathology, Harbor-UCLA Medical Center, Torrance, CA, USA
4 Present address: Quest Diagnostics, San Juan Capistrano, CA, USA
5 To whom correspondence should be addressed at: Department of Obstetrics and Gynecology, Harbor-UCLA Medical Center, 1000 West Carson Street, Box 489, Torrance, CA, USA. E-mail: okhorram{at}obgyn.humc.edu
Glycogen synthase kinase-3ß (GSK-3ß) is a serine/threonine kinase that plays a role in glycogen synthesis by inhibiting glycogen synthase (GS) through phosphorylation. We hypothesized that GSK-3ß by virtue of its role in glycogen synthesis through the inhibition of GS will play a role in the preparation of the endometrium for blastocyst implantation. Immunohistochemical (IHC) analysis and Western blot analysis (WBA) detected GSK-3ß in the endometrium, myometrium, Fallopian tube and ovary. WBA showed more than 5-fold higher endometrial expression of the phosphorylated GSK-3ß (pGSK-3ß) isoform (inactive) in the secretory phase as compared with the proliferative phase (P < 0.001), whereas no differences in total GSK-3ß expression were detected. IHC analysis confirmed the WBA and showed marked expression of pGSK-3ß predominantly in glandular epithelial cells in early and mid secretory endometrium with scant expression during the proliferative phase. In in vitro experiments using human endometrial-derived epithelial cell line (HES), progesterone did not alter total GSK mRNA or protein expression. However, progesterone induced a dose-dependent increase in the expression of pGSK-3ß, which could be blocked by RU486. Cyclic expression of GSK-3ß’s active and inactive forms in the endometrium suggests that sex hormones regulate the expression of this enzyme. In vitro experiments demonstrate that progesterone through receptor-mediated mechanisms induces phosphorylation of endometrial GSK-3ß.
Key words: endometrium/glycogen synthase kinase-3ß/menstrual cycle/progesterone/RU486