OPPOSING ACTIONS OF TRANSFORMING GROWTH-FACTOR-BETA AND GLUCOCORTICOIDS IN THE REGULATION OF FIBRONECTIN EXPRESSION IN THE HUMAN PLACENTA

Alterations in the expression of extracellular matrix (ECM) proteins i n the placenta and fetal membranes have been linked to parturition whe ther occurring before or at term. In the present study, we examined th e individual and combined effects of transforming growth factor (TGF)- beta and dexamethasone (DEX) on the expression of oncofetal fibronecti n (onfFN), i.e. a major ECM protein synthesized by placenta, in cytotr ophoblasts isolated from human term placentas to establish a model sys tem from which to evaluate the actions of positive and negative regula tors of ECM protein expression in the human placenta. Cytotrophoblasts were maintained for 21-62 h in medium supplemented with 4% charcoal-s tripped calf serum in the presence or absence of TGF-beta (2 ng/mL) an d DEX(10(-7) mol/L). Levels of onfFN in culture media were determined by immunoassay. TGF-beta treatment alone induced approximately a 150% increase in media levels of onfFN after 21 and 45 h of culture when co mpared with control, whereas DEX treatment alone reduced levels of onf FN to 15% of control levels. Media levels of onfFN in cells treated wi th both TGF-beta and DEX were 40-90% of control levels. Similarly, tre atment of cells with TGF-beta alone promoted a 100-250% increase in ra tes of FN synthesis and levels of FN messenger ribonucleic acid, where as DEX treatment alone reduced these indices of FN expression to appro ximately 10% of control levels. In cells treated with TGF-beta and DEX , levels of ECM protein synthesis and FN messenger ribonucleic acid we re between 30 and 100% of control values. Similar patterns of regulati on of FN expression by TGF-beta and DEX were observed when experiments were carried out in serum-free medium. Our results suggest that durin g pregnancy, TGF-beta and glucocorticoids may be important opposing ph ysiological regulators of placental ECM protein expression.