Malnutrition during pregnancy causes fetal growth retardation. Somatomedin/insulin-like growth factor (Sm/IGFs) are believed to stimulate fetal growth and differentiation, and nutrition is a principal regulator of serum Sm/IGFs in postnatal life. I hypothesize that the fetal growth retardation that results from maternal malnutrition is mediated in part by decreased production of Sm/IGFs in the fetus. I plan to deprive pregnant rats of nutrients, to study insulin-like growth factor I (IGF-I) and IGF-II production in their fetuses, and to correlate changes in Sm/IGFs with changes in total body and organ growth. IGF-I and IGF-II production will be assessed by measuring serum and tissue peptide concentrations and steady state levels of the mRNAs for these peptides. Because multiple mRNAs are expressed for both IGF-I and IGF-II in the fetus, I anticipate that specific changes in mRNA expression will produced by maternal nutrient deprivation. I propose, therefore, to determine Whether these changes are exon and/or promotor specific. Using transcription run-off assays, I also propose to determine whether changes in Sm/IGF mRNAs are mediated at the level of gene transcription. Because the nature of the precursor Sm/IGF encoded by these mRNAs is not known, I will use in vitro translation techniques to determine if nutrient deprivation causes expression of IGF-I and IGF-II precursor proteins different from those in fully fed animals. The objectives defined in this proposal represent an extension of my interest in fetal growth, which was spawned during my pediatric residency and fostered during my fellowship in pediatric endocrinology in a laboratory in which the Sm/IGFs have been the major focus for nearly two decades. My studies will provide new information on regulation of somatomedins in the fetus and the role of the Sm/IGFs in fetal growth. These studies should also provide me with the opportunity to expand my research experience.
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