9317132 Chen Insulin-like growth factors (IGFs) are small peptide hormones known to play important roles in regulating growth and differentiation of vertebrates. Studies conducted in mammals showed that IGF-II is produced in the liver and several other prenatal and neonatal tissues, whereas IGF-I is primarily produced in the post-natal livers under the control of growth hormone (GH). However, the mechanism of hormonal regulation of IGF-I and IGF-II gene expression has not been determined. Using rainbow trout as experimental animals, the long term objective of this research is to investigate the molecular mechanism of GH controlled IGF gene expression. To achieve this long term objective, a list of short term aims has been developed for the next three years. These are: (1) determining patterns of tissue and developmental stage specific expression of IGF genes; (2) identifying hormonal factors that regulate the expression of IGF genes in vivo and in vitro; (3) assessing the consequence of differential inactivation of the production of IGF-I or IGF-II polypeptide by a combination of transgenic fish and Ribozyme technologies; (4) isolating and characterizing the GH receptor and its cDNA molecules. Fish represent the largest and the most diverse group of vertebrates and their unique evolutionary position relative to other vertebrates and their ability to adapt to a wide variety of environments make them ideal for studying the molecular mechanisms of growth regulation. Results of these proposed studies will advance the knowledge of vertebrate IGF gene regulation and expression in a way that is both easily generalized to vertebrate models, and will provide a phylogenetic perspective that has proved useful in the studies of other complex biological phenomena. Furthermore, these studies on GH modulated IGF gene expression in fish will provide an excellent alternative model for studying the control of growth factor gene expression at the molecular level in hu mans. ***
