Effect of cytokines and growth factors on the secretion of inhibin A, activin A and follistatin by term placental villous trophoblasts in culture.

Journal article

OBJECTIVE: Maternal serum inhibin A and activin A are higher in pre-eclampsia than in normal pregnancy. The placenta is a source of these proteins in pregnancy. The aim of this study was to investigate the effect of growth factors and proinflammatory cytokines that are raised in pre-eclampsia on the secretion of dimeric inhibin A, activin A and follistatin by villous cytotrophoblasts in culture. DESIGN AND METHODS: Villous cytotrophoblasts were prepared from term placentae and cultured in serum-free media. Cells were treated with increasing concentrations of tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, transforming growth factor (TGF)-beta1, granulocyte and monocyte colony-stimulating factor (GMCSF), inhibin A, activin A and follistatin for 2 days. Culture supernatants were assayed for human chorionic gonadotrophin (hCG), inhibin A, activin A and follistatin as appropriate. Experiments were repeated at least three times with each cytokine or growth factor and the data pooled. RESULTS: Cytotrophoblasts syncytialise and spontaneously secrete hCG, inhibin A and activin A in culture. Follistatin levels were <20 pg/ml in most experiments. Activin A secretion was increased in culture in a dose-dependent manner by IL-1beta (approximately 150%, P<0.05), TNF-alpha (approximately 35%, P=0.02) and GMCSF (approximately 100%, P<0.01). hCG secretion was inhibited in a dose-dependent manner by TNF-alpha (50%, P<0.05). Inhibin A was stimulated by IL-1beta ( approximately 30%, P=0.05). Inhibin A, activin A, follistatin or TGF-beta1 did not have a significant effect on any measured parameters. CONCLUSIONS: These data show that inflammatory cytokines increase the secretion of activin A by trophoblasts in culture. The presence of very low levels, or no follistatin (<20 pg/ml) in the culture media suggests 'free' activin A could have autocrine/paracrine effects on cytotrophoblasts. Inhibin A secretion was stimulated by IL-1beta. However, absence of an effect by the other cytokines investigated on inhibin A in this study suggests that the mechanism(s) involved in increasing maternal circulating levels of inhibin A and activin A in pre-eclampsia are controlled differentially.

Authors: Mohan, A; Asselin, J; Sargent, I; Groome, N; Muttukrishna, S

• Publication status: Published
• Journal: European journal of endocrinology / European Federation of Endocrine Societies
• Volume: 145
• Issue: 4
• Pages: 505-511
• Publication date: 2001-10-01
• DOI: 10.1530/eje.0.1450505
• EISSN: 1479-683X
• ISSN: 0804-4643
• Language: English
• Keywords: Cells, Cultured; Chorionic Villi; Pregnancy; Inhibins; Granulocyte-Macrophage Colony-Stimulating Factor; Inhibin-beta Subunits; Interleukin-1; Transforming Growth Factor beta; Humans; Trophoblasts; Follistatin; Cytokines; Activins; Female; Placenta; Tumor Necrosis Factor-alpha; Growth Substances