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

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-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), on the regulation of IGF-II gene expression in cultured HFA cells. Both TNF-alpha and IFN-gamma inhibited basal and ACTH-induced accumulation of IGF-II mRNA dose-dependently. Cell viability was not altered by treatment with TNF-alpha or IFN-gamma. In addition, the combination of TNF-alpha and IFN-gamma decreased ACTH-induced IGF-II mRNAs more potently than each cytokine alone. Our results suggest that TNF-alpha and IFN-gamma may be involved in the regulation of HFA growth and differentiation via local IGF-II production.