Regulation of insulin like growth factor I gene expression - Implications for normal and pathological growth

Insulin-like growth factor I (IGF-I) is a 70-amino acid peptide growth factor of which the synthesis is required in order for the normal rate and magnitude of growth to be achieved and maintained. IGF-I is synthesized and released from the liver in the postnatal period and mediates much of growth hormone (GH) action. In addition, significant expression of IGF-I in extrahepatic tissues serves an autocrine/paracrine function throughout fetal and postnatal life. IGF-I gene expression is highly correlated with systemic growth and with numerous tissue-specific growth, differentiation, and remodeling programs, Nutritional sufficiency and adequate GH and insulin levels signal IGF-I transcription and growth, whereas catabolic states downregulate IGI-I transcription and lead to growth retardation. Upregulation of IGF-I gene expression occurs during brain, adipose, muscle, bone, and hematopoietic differentiation. Compensatory IGF-I gene expression also occurs in response to injury, and increased IGF-I expression may be a component of pathological cardiovascular and kidney remodeling scenarios. The complex pattern of IGF-I gene expression involves transcription from two promoters that give rise to an array of IGF-I mRNAs with different 5'-untranslated regions (UTRs), different 3'-UTRs, and different signal and trailer peptide coding regions. Thus, IGF-I gene expression is potentially regulated at transcriptional and post-transcriptional levels. Regions of IGF-I gene important in transcriptional regulation and GH and developmental induction of transcription are beginning to be defined.