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Regulation of Activin A, Inhibin A, and Follistatin Production in Human Amnion and Choriodecidual Explants by Inflammatory Mediators

Department of Pharmacology and Clinical Pharmacology, University of Acukland Faculty of Medical and Health Sciences, Auckland, New Zealand; School of Biological Molecular Sciences, Oxford Brookes University, Headington, Oxford, United Kingdom; j.keelan{at}auckland.ac.nz

Ren Li Zhou, MSc

Lee W. Evans, PhD

Nigel P. Groome, PhD

Murray D. Mitchell, DSc

Department of Pharmacology and Clinical Pharmacology, University of Acukland Faculty of Medical and Health Sciences, Auckland, New Zealand; School of Biological Molecular Sciences, Oxford Brookes University, Headington, Oxford, United Kingdom

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 chroidecidual tissues.

Methods: The effects of interleukin-1ß (IL-1ß; 1 ng/mL), tumor necrosis factor- (TNF-; 10 ng/mL), and bacterial lipopolysaccharide (LSP; 5 µg/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-1ß and TNF- 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 inhibition 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.

Key Words: Activin • inhibin • follistatin • cytokines • parturition

Journal of the Society for Gynecologic Investigation, Vol. 7, No. 5, 291-296 (2000)
DOI: 10.1177/107155760000700504


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