CELLULAR AND CLINICAL PERSPECTIVES ON SKELETAL INSULIN-LIKE GROWTH-FACTOR-I

Insulin-like growth factor (IGF) I, a polypeptide synthesized by skele tal cells, is presumed to act as an autocrine regulator of bone format ion. IGF I stimulates bane replication of preosteoblastic cells and en hances the differentiated function of the osteoblast. The synthesis of skeletal IGF I is regulated by systemic hormones, most notably parath yroid hormone and glucocorticoids, as well as by locally produced fact ors, such as prostaglandins and other skeletal growth factors. Whereas hormones and growth factors regulate IGF I synthesis, the exact level of regulation has not been established and may involve both transcrip tional and posttranscriptional mechanisms. The IGF I gene contains six exons, and both exon 1 and 2 contain transcription initiation sites. Extrahepatic tissues, including bone, express exon 1 transcripts, and regulation of the exon 1 promoter activity in osteoblasts is currently under study. It is apparent that the regulation of IGF I gene transcr iption as well as the regulation of mRNA stability is complex and tiss ue specific. It is possible that abnormalities in skeletal IGF I synth esis or activity play a role in the pathogenesis of bone disorders. In view of its important anabolic actions in bone, it is tempting to pos tulate the use of IGF I for the treatment of disorders characterized b y decreased bone mass. An alternative could be the stimulation of the local production of IGF I in bone. (C) 1994 Wiley-Liss, Inc.