TRANSFORMING GROWTH-FACTOR-BETA STIMULATES, AND GLUCOCORTICOIDS AND EPIDERMAL GROWTH-FACTOR INHIBIT BRAIN NATRIURETIC PEPTIDE SECRETION FROM CULTURED HUMAN AMNION CELLS

We previously reported the massive secretion of brain natriuretic pept ide (BNP) from human amnion cells and suggested the possible role of B NP in the maintenance of human pregnancy. In this study, to elucidate the regulatory mechanism of BNP secretion from amnion cells, we measur ed the BNP level in the culture medium of amnion cells by RIA after in cubation in the presence of various substances. Among the agents exami ned, cortisol (1 x 10(-7) to 1 X 10(-6) mol/L), dexamethasone (1 x 10( -8) to 1 x 10(-6) mol/L), and epidermal growth factor (EGF; 2 x 10(-11 ) to 2 x 10(-8) mol/L) inhibited BNP secretion from the cultured amnio n cells in a dose-dependent manner. By contrast, transforming growth f actor-beta (TGF beta; 4 x 10(-11) to 4 x 10(-9) mol/ L) caused a 3- to 5-fold increase in BNP secretion. TGF beta-augmented BNP secretion wa s abolished by the addition of cortisol or EGF to the culture medium. Moreover, in this study, we revealed the presence of bioactive TGF bet a in human amniotic fluid (similar to 4 x 10(-10) mol/L). The present finding of tight regulation of BNP secretion from amnion cells by cort isol, EGF and TGF beta, all at the concentrations physiologically pres ent in human amniotic fluid, implies a physiological role of BNP secre tion from amnion cells in the pregnant uterus.