title: Developmental regulation of glucocorticoid-mediated effects on extracellular matrix protein expression in the human placenta.
abstract: The extracellular matrix (ECM) protein fibronectin (FN) is a critical regulator of uterine-placental adherence. In the present report we compared the effects of glucocorticoids on FN expression in cytotrophoblast cultures isolated from human first trimester and term placentas to elucidate potential steroid-dependent cellular mechanisms associated with human parturition. Based on immunoassays, treatment of first trimester cytotrophoblasts with 10(-7) M dexamethasone (DEX) for 2 cr 4 days reduced medium levels of oncofetal FN (onfFN; i.e. FNs bearing an oncofetal epitope) to approximately 80% of control levels. Conversely, treatment of cytotrophoblasts isolated from term placentas with DEX dramatically reduced medium levels of onfFN to approximately 12% of control values. Treatment of both first trimester and term cells with 10(-6) M progestin, mineralocorticoid, or estrogen had no significant effect on onfFN expression in either cell type. Glucocorticoids specifically down-regulated medium levels of onfFN in term cells, but not in first trimester cells. In contrast, DEX treatment promoted an approximately 3- to 7-fold increase in levels of hCG in both first trimester and term cytotrophoblasts, suggesting that the effects of glucocorticoid on FN and hCG expression are elicited through independent cell-signaling pathways. In first trimester cells, DEX promoted a reduction in rates of FN and laminin synthesis to 60-70% of control levels. In term cells, DEX treatment reduced levels of FN and laminin synthesis to approximately 10% of control levels. Similarly, DEX treatment down-regulated levels of FN mRNA to approximately 60% and 10% of control values in first trimester and term cells, respectively. The first trimester of human pregnancy is associated with low levels of glucocorticoids and reduced glucocorticoid responsiveness. These conditions would favor high levels of placental ECM protein synthesis, thus stabilizing uterine-placental adherence. Conversely, elevated levels of glucocorticoids near parturition and increased glucocorticoid responsiveness would inhibit placental ECM protein synthesis, reducing uterine-placental adherence and promoting the separation of placenta from uterus.
authors.affiliation: Department of Obstetrics/Gynecology and Reproductive Science, Mt. Sinai Medical Center, New York, New York 10029.
authors.forename: S
authors.initials: S
authors.lastname: Guller
authors.forename: L
authors.initials: L
authors.lastname: Markiewicz
authors.forename: R
authors.initials: R
authors.lastname: Wozniak
authors.forename: J M
authors.initials: JM
authors.lastname: Burnham
authors.forename: E Y
authors.initials: EY
authors.lastname: Wang
authors.forename: P
authors.initials: P
authors.lastname: Kaplan
authors.forename: C J
authors.initials: CJ
authors.lastname: Lockwood
mesh_terms: D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology*; D005314:Embryonic and Fetal Development; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D005353:Fibronectins / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007797:Laminin / Q000235:genetics; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D014327:Trophoblasts / Q000378:metabolism
chemical_list: D006063:Chorionic Gonadotropin; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D007797:Laminin; D012333:RNA, Messenger; D003907:Dexamethasone