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 production of activin A, inhibin A, and the binding protein follistatin in term amnion and choriodecidual tissues.


METHODS
The effects of interleukin-1 beta (IL-1 beta; 1 ng/mL), tumor necrosis factor-alpha (TNF-alpha; 10 ng/mL), and bacterial lipopolysaccharide (LPS; 5 microg/mL) on production rates of activin A, inhibin A, and follistatin by term choriodecidual and amnion membranes in explant culture were determined using specific enzyme-linked immunoabsorbent assays.


RESULTS
All explants (n = 6 placentas) produced detectable amounts of activin A, inhibin A, and follistatin under basal conditions; choriodecidual production rates were more 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 +/- standard error of the mean; P <.05 by analysis of variance), whereas production of inhibin and follistatin was stimulated to a much more modest extent. Similar responses were observed in the choriodecidual explants. Lipopolysaccharide had no significant effect on amnion activin A production, but stimulated choriodecidual production to 290 +/- 34% of control. Lipopolysaccharide exerted only limited effects on inhibin A and follistatin production.


CONCLUSIONS
Treatment with proinflammatory mediators resulted in a preferential increase in activin A production compared with that of inhibin A or follistatin. These findings suggest that inflammation of the gestational membranes could result in increased local activin A production and bioactivity.
Keelan
J A
JA
Department of Pharmacology and Clinical Pharmacology, University of Auckland Faculty of Medical and Health Sciences, Auckland, New Zealand.j.keelan@auckland.ac.nz
Zhou
R L
RL
Evans
L W
LW
Groome
N P
NP
Mitchell
M D
MD
D028341:Activins; D000650:Amnion / Q000378:metabolism; D002823:Chorion / Q000378:metabolism; D046508:Culture Techniques; D016207:Cytokines / Q000494:pharmacology*; D003656:Decidua / Q000378:metabolism*; D005321:Extraembryonic Membranes / Q000378:metabolism*; D005260:Female; D038681:Follistatin; D006023:Glycoproteins / Q000096:biosynthesis*; D006801:Humans; D007265:Inhibins / Q000096:biosynthesis*; D007375:Interleukin-1 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D038681:Follistatin; D006023:Glycoproteins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D028341:Activins; D007265:Inhibins