DEVELOPMENTAL REGULATION OF GLUCOCORTICOID-MEDIATED EFFECTS ON EXTRACELLULAR-MATRIX PROTEIN EXPRESSION IN THE HUMAN PLACENTA

Citation
S. Guller et al., DEVELOPMENTAL REGULATION OF GLUCOCORTICOID-MEDIATED EFFECTS ON EXTRACELLULAR-MATRIX PROTEIN EXPRESSION IN THE HUMAN PLACENTA, Endocrinology, 134(5), 1994, pp. 2064-2071
Citations number
40
Categorie Soggetti
Endocrynology & Metabolism
Journal title
ISSN journal
00137227
Volume
134
Issue
5
Year of publication
1994
Pages
2064 - 2071
Database
ISI
SICI code
0013-7227(1994)134:5<2064:DROGEO>2.0.ZU;2-N
Abstract
The extracellular matrix (ECM) protein fibronectin (FN) is a critical regulator of uterine-placental adherence. In the present report we com pared the effects of glucocorticoids on FN expression in cytotrophobla st cultures isolated from human first trimester and term placentas to elucidate potential steroid-dependent cellular mechanisms associated w ith human parturition. Based on immunoassays, treatment of first trime ster cytotrophoblasts with 10(-7) M dexamethasone (DEX) for 2 or 4 day s reduced medium levels of oncofetal FN (onfFN; i.e. FNs bearing an on cofetal epitope) to approximately 80% of control levels. Conversely, t reatment of cytotrophoblasts isolated from term placentas with DEX dra matically reduced medium levels of onfFN to approximately 12% of contr ol values. Treatment of both first trimester and term cells with 10(-6 ) M progestin, mineralocorticoid, or estrogen had no significant effec t on onfFN expression in either cell type. Glucocorticoids specificall y down-regulated medium levels of onfFN in term cells, but not in firs t trimester cells. In contrast, DEX treatment promoted an approximatel y 3- to 7-fold increase in levels of hCG in both first trimester and t erm 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 cell s, DEX treatment reduced levels of FN and laminin synthesis to approxi mately 10% of control levels. Similarly, DEX treatment down-regulated levels of FN mRNA to approximately 60% and 10% of control values in fi rst trimester and term cells, respectively. The first trimester of hum an pregnancy is associated with low levels of glucocorticoids and redu ced glucocorticoid responsiveness. These conditions would favor high l evels of placental ECM protein synthesis, thus stabilizing uterine-pla cental 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.