Glucocorticoid suppression of human placental fibronectin expression: implications in uterine-placental adherence.
Increased levels of glucocorticoids are associated with human parturition whether occurring before or at term. In the present study we examined the effects of glucocorticoids on placental fibronectin (FN) expression in cytotrophoblasts, isolated from human term placentas, to provide a potential mechanism through which glucocorticoids may influence uterine-placental adherence near parturition. Based on immunoassays, relative to controls, media levels of placental FNs bearing an oncofetal epitope (onfFN) were inhibited 65-80% by treatment with 10(-7) M dexamethasone (DEX) during experiments in which cumulative levels and daily release of onfFN were measured. DEX treatment increased human CG production by cytotrophoblasts approximately 3-fold without affecting the levels of total protein, suggesting that DEX treatment did not reduce placental function. DEX and cortisol inhibited onfFN expression with an EC50 of 2 and 16 nM, respectively. Other steroids were not effective in down-regulating onfFN expression, indicating that this was a glucocorticoid-specific response. In immunoprecipitation studies, treatment of cytotrophoblasts with 10(-7) M DEX for 3 days inhibited both release of labeled FN to the media and its incorporation into cell-associated material by approximately 80%. Results from Northern blotting indicated that DEX treatment suppressed levels of FN messenger RNA approximately 90% relative to controls. Levels of labeled laminin in media were inhibited approximately 80% by a 3-day treatment with 10(-7) M DEX, suggesting that glucocorticoids may coordinately suppress the synthesis of multiple extracellular matrix proteins in cytotrophoblasts. In our model, we propose that glucocorticoids may suppress placental extracellular matrix protein synthesis, which could lead to decreased uterine-placental adherence and be associated with parturition.
Guller
S
S
Department of Obstetrics/Gynecology and Reproductive Science, Mount Sinai Medical Center, New York, New York 10029.
Wozniak
R
R
Krikun
G
G
Burnham
J M
JM
Kaplan
P
P
Lockwood
C J
CJ
D015152:Blotting, Northern; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005353:Fibronectins / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007163:Immunosorbent Techniques; D015735:Mifepristone / Q000494:pharmacology; D009693:Nucleic Acid Hybridization; D010920:Placenta / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism; D014599:Uterus / Q000502:physiology*
D006063:Chorionic Gonadotropin; D005353:Fibronectins; D005938:Glucocorticoids; D012333:RNA, Messenger; D015735:Mifepristone; D003907:Dexamethasone; D006854:Hydrocortisone