Regulation of the lGF System by Glucocortidoids

Insulin-like growth factors (IGFs) play a pivotal role in promoting embryonic and fetal growth, and display a wider range of developmental and tissue specific expression than any other growth factors. Glucocorticoids exert a variety of anabolic and catabolic effects and are involved in the organisms response to stress. During development, there appears to be a co-ordinated regulation of glucocorticoid biosynthesis and IGF gene expression in the embryo. In particular, attention has been focussed on the role of the glucocorticoid surge just before birth in regulating IGF levels in the embryo. IGFs and glucocorticoids have been known to have corroborating effects on cell proliferation, with glucocorticoids affecting IGFs at a transcriptional level. The purpose of this review, then, is to collate the current knowledge of how glucocorticoids can effect regulation of IGFs, both directly and via regulation of the IGF receptors and binding proteins, which themselves regulate IGFs and their effects. We show that this regulation is complex and bi-directional, occurring in different tissue types to up- or downregulate levels of IGF or IGF-binding protein transcription or protein levels, intricately linking the glucocorticoids to the insulin like growth factors in the control of cell growth and proliferation.