Expression of endometrial glycogen synthase kinase-3beta protein throughout the menstrual cycle and its regulation by progesterone.
Glycogen synthase kinase-3beta (GSK-3beta) is a serine/threonine kinase that plays a role in glycogen synthesis by inhibiting glycogen synthase (GS) through phosphorylation. We hypothesized that GSK-3beta 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-3beta in the endometrium, myometrium, Fallopian tube and ovary. WBA showed more than 5-fold higher endometrial expression of the phosphorylated GSK-3beta (pGSK-3beta) isoform (inactive) in the secretory phase as compared with the proliferative phase (P < 0.001), whereas no differences in total GSK-3beta expression were detected. IHC analysis confirmed the WBA and showed marked expression of pGSK-3beta 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-3beta, which could be blocked by RU486. Cyclic expression of GSK-3beta'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-3beta.
Salameh
Wael
W
Department of Internal Medicine, Harbor-UCLA Medical Center, Torrance, CA, USA.
Helliwell
Jason P
JP
Han
Guang
G
McPhaul
Laron
L
Khorram
Omid
O
D000328:Adult; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004717:Endometrium / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology; D005260:Female; D006003:Glycogen / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D008597:Menstrual Cycle / Q000378:metabolism*; D015735:Mifepristone / Q000494:pharmacology; D010766:Phosphorylation; D011374:Progesterone / Q000037:antagonists & inhibitors / Q000378:metabolism*
D006727:Hormone Antagonists; D015735:Mifepristone; D011374:Progesterone; D006003:Glycogen; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3