REDUCTION OF EXTRACELLULAR-MATRIX PROTEIN EXPRESSION IN HUMAN AMNION EPITHELIAL-CELLS BY GLUCOCORTICOIDS - A POTENTIAL ROLE IN PRETERM RUPTURE OF THE FETAL MEMBRANES

Low levels of expression of extracellular matrix (ECM) proteins in cho rioamniotic membranes is a characteristic of prematurely ruptured memb ranes, a condition associated with 40% of preterm deliveries. In light of the rise ill levels of glucocorcicoids (GC) in amniotic fluid asso ciated with preterm labor, in the present study we examined the effect s of GC on the expression of major ECM proteins in cultures of amnion epithelial cells recovered after digestion of human term amnions. Amni on cells were maintained with and without 10(-7) mol/L dexamethasone ( DEX), and levels of the ECM protein fibronectin (FN) were determined b y enzyme-linked immunosorbent assay. DEX treatment reduced FN expressi on, in amnion epithelial cells to 15-30% of control levels and reduced FN expression in placental cells to 30-50% of control levels. Convers ely, DEX treatment weakly stimulated FN expression in chorion cell cul tures DEX treatment did not affect the total level of amnion cell prot ein, indicating that the effects of DEX in amnion cells did not result from a general reduction in protein synthesis. Cortisol and DEX reduc ed FN expression in amnion cells, with half-maximal effective concentr ations of approximately 60 and 8 nmol/L, respectively. In immunoprecip itation studies, DEX treatment reduced FN and collagen III synthesis t o 20% of control levels, suggesting that GC may coordinately reduce th e synthesis of major ECM proteins in amnion cells. Similarly, DEX trea tment reduced the levels of FN messenger ribonucleic acids in amnion c ells to approximately 15%; of control levels. DEX treatment also promo ted a marked reduction in FN expression in amnion cells cultured in se rum-free medium to 10-50% of control levels. Our results indicate that GC negatively regulate ECM protein expression in amnion epithelial ce lls, suggesting a potential role in the genesis of altered fetal membr ane ECM protein expression associated with prematurely ruptured membra nes.