Function and Regulation of IGF-I, IGF-II and IGF Type I Receptor Genes in Lower Vertebrates

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Insulin-like growth factors (IGFs) are mitogenic and anabolic peptide hormones that play an important role in growth and differentiation of vertebrates. Results of numerous studies in mammals suggest that while IGF-II is produced in the liver and several other pre-natal and neonatal tissues, IGF-I is produced in the post-natal livers under the modulation of growth hormone (GH). The long-term goals of this project are to investigate the function and regulation of IGF-I, IGF-II and IGF type I receptor genes on development and growth, using rainbow trout as model experimental animals. In the previous funding cycle, this investigator has shown that: (a) a cis-acting element, C/EBP binding site, is present in the promoter region of the IGF II gene, and C/EBPs are inducible by GH, and (b) mRNA of IGF-I, IGF-II, IGF type I are present in eggs as maternal mRNA, and are differentially expressed during embryonic development. These results suggest that GH, IGF-I, IGF-II and IGF type I receptor play important roles during trout embryonic development and growth. To delineate the functions of these factors, the PI will address the following questions in the next three years: (1) How do the CCAAT cis-acting elements and their hepatic nuclear binding proteins (C/EBPs) regulate the expression of IGF-II by GH? (2) In addition to GH, are there any other hormonal factors such as prolactin, insulin, estrogen, testosterone and thyroid hormone that may regulate the expression of fish IGF-II gene via modulation by the CCAAT cis-acting elements and their hepatic nuclear binding proteins (C/EBPs)? (3) Are both IGFRa and IGFRb biologically active?