Tumor necrosis factor-α and interferon-γ inhibit insulin-like growth factor II gene expression in human fetal adrenal cell cultures

Abstract

Insulin-like growth factor-II (IGF-II) gene expression is induced by adrenocorticotropic hormone (ACTH) in human fetal adrenals (HFA), which suggests an important role for IGF-II in HFA growth and differentiation. Many cytokines have different regulatory actions in the endocrine glands. In the present study we have investigated the effects of two cytokines, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), on the regulation of IGF-II gene expression in cultured HFA cells. Both TNF-α and IFN-γ inhibited basal and ACTH-induced accumulation of IGF-II mRNA dose-dependently. Cell viability was not altered by treatment with TNF-α or IFN-γ. In addition, the combination of TNF-α and IFN-γ decreased ACTH-induced IGF-II mRNAs more potently than each cytokine alone. Our results suggest that TNF-α and IFN-γ may be involved in the regulation of HFA growth and differentiation via local IGF-II production.