Regulation of activin A, inhibin A, and follistatin production in human amnion and choriodecidual explants by inflammatory mediators

OBJECTIVE: To determine the effects of inflammatory mediators on the produc tion of acfivin A, inhibin A, and the binding protein follistatin in term a mnion and choriodecidual tissues. METHODS: The effects of interleukin-1 beta (IL-1 beta; 1 ng/mL), tumor necr osis factor-alpha (TNF-alpha; 10 ng/mL), and bacterial lipopolysaccharide ( LPS; 5 mu g/mL) on production rates of activin A, inhibin A, and follistati n by term choriodecidual and amnion membranes in explant culture were deter mined using specific enzyme-linked immunoabsorbent assays. RESULTS: All explants (n = 6 placentas) produced detectable amounts of acti vity A, inhibin A, and follistatin under basal conditions; choriodecidual p roduction rates were move than tenfold higher than amnion rates. In amnion explants, activin A production was stimulated by IL-1 beta and TNF-alpha to 450 +/- 155.4% and 531 +/- 170.8% of control, respectively (mean +/- stand ard error of the mean; P < .05 by analysis of variance), whereas production of inhibin and follistatin runs stimulated to a much more modest extent. S imilar responses were observed in the choriodecidual explants. Lipopolysacc haride had no significant effect on amnion activin A production, but stimul ated choriodecidual production to 290 +/- 34% of control. Lipopolysaccharid e exerted only limited effects on inhibin A and follistatin production. CONCLUSIONS: Treatment with proinflammatory mediators resulted in a prefere ntial increase in acfivin A production compared with that of inhibin A or f ollistatin. These findings suggest that inflammation of the gestational mem branes could result in increased local activin A production and bioactivity . Copyright (C) 2000 by the Society for Gynecologic Investigation.