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  • Title: Role of activin A as a mediator of in vitro endometrial stromal cell decidualization via the cyclic adenosine monophosphate pathway.
    Author: Tierney EP, Giudice LC.
    Journal: Fertil Steril; 2004 Mar; 81 Suppl 1():899-903. PubMed ID: 15019827.
    Abstract:
    OBJECTIVE: To elucidate the regulation and role of activin A in endometrial stromal decidualization. DESIGN: In vitro model of human stromal cell decidualization with cyclic adenosine monophosphate (cAMP) used to evaluate expression of activin A and to evaluate the effect of the addition of follistatin, a known activin inhibitor, on expression of the decidualized phenotype (as measured by levels of insulin-like growth factor binding protein-1 [IGFBP-1]). SETTING: Academic research environment. PATIENT(S): Four premenopausal, normally cycling subjects (age range: 32-40 years). INTERVENTION(S): Endometrial samples were obtained from the subjects after informed consent was obtained. Endometrial stromal cells were treated with cAMP (decidualizing stimulus) and 50 ng/mL, 100 ng/mL, and 200 ng/mL of follistatin for 48 hours. MAIN OUTCOME MEASURE(S): Levels of IGFBP-1 secreted from cells decidualized in the absence and presence of three different concentrations of follistatin. RESULT(S): Addition of follistatin, a known binding protein inhibitor of activin A, resulted in a dose-dependent inhibition of IGFBP-1 secreted into conditioned medium, with the greatest decrease observed at 4 days of decidualization. Cells treated with cAMP and 50 ng/mL, 100 ng/mL, and 200 ng/mL of follistatin demonstrated 67.3%, 58.6%, and 35.5%, respectively, of the IGFBP-1 levels observed with cAMP but without follistatin. CONCLUSION(S): These data suggest that activin A is a necessary component of the cAMP pathway leading to endometrial stromal decidualization. The role of activin A in regulating endometrial stromal decidualization and its known promotion of the invasive phenotype of the trophoblast suggest unique autocrine and paracrine interactions at the maternal/fetal interface during implantation, which might have important clinical implications for the understanding and treatment of fertility and pregnancy disorders.
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