ROLE OF INSULIN-LIKE GROWTH-FACTORS IN STEROID MODULATED PROLIFERATION

The mechanism by which steroids influence cell proliferation is poorly understood although an understanding of this process might facilitate the development of strategies to modulate the tissue-specific activit y of steroid hormones. In this article, the evidence that steroid horm ones interact with the insulin-like growth factor (IGF) signal transdu ction pathway is reviewed for three different tissues. In osteoblasts, oestradiol stimulates the production of IGF-I which appears to act as an autocrine growth factor. In uterine tissue, oestradiol increases t he synthesis of IGF-I in the stroma which then modulates the prolifera tion of epithelial cells although there is also evidence that oestradi ol can modulate the sensitivity of uterine epithelial cells to IGFs. I n breast cancer, oestrogens may increase IGF-II synthesis in epithelia l cells, increase the sensitivity of breast cancer cells to IGFs (poss ibly by modulating type I IGF receptor levels) as well as resulting co mponents of the IGF signal transduction pathway resulting in induction of immediate early genes. There therefore appears to be a variety of ways in which oestradiol interact with the IGF signal transduction pat hway and these may be applicable to other malignant and normal tissues and other groups of steroid hormones.