Insulin-like growth factor I and bone: from mouse to man.

Serum insulin-like growth factor I (IGF-I) is regulated by numerous variables, including growth hormone (GH), nutritional status, gonadal steroids and other hormones. However, the circulating IGF-I phenotype is also under heritable regulation, and several genetic determinants may be important in defining tissue-specific expression of the gene encoding this peptide. A very strong correlation has been found between serum IGF-I concentration and bone acquisition in both mice and humans. Based on previous studies as well as ongoing work with mice, it has been hypothesized that regulation of the serum IGF-I phenotype includes non-GH-dependent factors and, furthermore, that these determinants are also involved in the acquisition of bone mass. This paper reports that, by performing intercrosses between two inbred strains of mice of similar age, size and length, but with different serum levels of IGF-I, we have identified regulatory loci for serum IGF-I and established their relationship to putative quantitative trait loci for bone mineral density. Mapping these quantitative trait loci will help refine our understanding of disorders related to IGF-I.