Physiology of insulin-like growth factor 1
- David R Clemmons, MD
David R Clemmons, MD
- Distinguished Professor of Medicine
- University of North Carolina School of Medicine
Insulin-like growth factor 1 (IGF-1) is a hormone that functions as the major mediator of growth hormone (GH)-stimulated somatic growth, as well as a mediator of GH-independent anabolic responses in many cells and tissues. IGF-1 is a small peptide (molecular weight 7647) that circulates in serum bound to high affinity binding proteins. IGF-1 is an unusual peptide in this regard, since it is more than 99 percent protein-bound.
IGF-1 is synthesized by multiple mesenchymal cell types. As a result, there are two major mechanisms of IGF-1 regulation:
●IGF-1 that is synthesized in the liver and secreted into the blood is under the control of GH.
●Autocrine/paracrine IGF-1 synthesized in peripheral tissues, such as bone. Its synthesis is controlled by GH and by factors that are secreted locally by the surrounding cell types. Since some of the autocrine/paracrine IGF-1 that is secreted enters into the systemic circulation, understanding the factors that regulate its synthesis is necessary to interpret changes in serum IGF-1 concentrations.
IGF-1 exerts its effects via activation of the IGF-1 receptor . This receptor is widely distributed, which enables blood-transported IGF-1 to coordinate balanced growth among multiple tissues and organs. In contrast, autocrine/paracrine IGF-1 can stimulate local, unbalanced growth independently of systemic GH. Examples of this type of growth regulation are wound healing and growth of the contralateral kidney after unilateral nephrectomy.
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- IGF GENES AND STRUCTURE
- IGF-1 RECEPTORS
- IGF-1 receptor
- - Receptor activation
- IGF-2/mannose 6 phosphate receptor
- IGF BINDING PROTEINS
- Structural differences
- Regulation of plasma IGFBPs
- - IGFBP-3
- - IGFBP-2
- - IGFBP-1
- - IGFBP-4 and -5
- REGULATION OF CIRCULATING IGF-1
- Growth hormone
- Nutritional status
- Other hormones
- REGULATION OF TISSUE IGF-1
- MAJOR PHYSIOLOGIC EFFECTS OF IGF-1
- Whole animal studies
- Transgenic animal models
- Effects of IGF-1 administration to humans
- MECHANISMS OF ACTION OF IGF-1