Glucocorticoid receptor function suppresses insulin-like growth factor 1 activity in human KLE endometrial-like cells.
We analysed the glucocorticoid receptor (GR) regulation on the expression of insulin-like growth factor 1 (IGF-1), type I IGF receptor (IGF-1.R), IGF-binding protein 3 (IGFBP-3), urokinase-type plasminogen activator (uPA) and uPA receptor (uPA.R) mRNA in human KLE endometrial-like cells. We documented that KLE cells express IGF-1, IGF-1.R, uPA and IGFBP-3 mRNA, however not uPA.R mRNA. Exogenous administration of dexamethasone inhibited the proliferation of KLE cells without inducing apoptosis. The inhibition of dexamethasone on KLE cell proliferation was neutralized by exogenous administration of IGF-1. Furthermore, dexamethasone suppressed the expression of IGF-1 mRNA and IGF-1.R mRNA as well as the IGF-1 bioavailability in KLE cell culture media, but it did not alter the expression of uPA mRNA and IGFBP-3 mRNA in KLE cells. Since the peritoneal fluid of women with endometriosis is known to contain IGF-1, which stimulates the proliferation and inhibits the apoptosis of endometrial-like cells, it is conceivable that GR-mediated down-regulation of IGF-1 bioavailability may be of clinical relevance for endometriosis.
Lembessis
Peter
P
Department of Experimental Physiology, Medical School, University of Athens, Goudi-Athens, 115 27 Greece.
Kalariti
Niki
N
Koutsilieris
Michael
M
D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D004717:Endometrium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000502:physiology*; D055293:Receptors, Urokinase Plasminogen Activator
C524898:PLAUR protein, human; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011965:Receptors, Glucocorticoid; D055293:Receptors, Urokinase Plasminogen Activator; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone; D017526:Receptor, IGF Type 1