George Lamson

Insulin-like growth factor binding proteins: structural and molecular relationships.

AbstractThe insulin-like growth factors (IGFs) are important metabolic and mitogenic factors involved in cell growth and metabolism. IGF-I and -II belong to a family of peptide hormones that include relaxin and insulin, and they share a high degree of structural similarity with proinsulin. They are produced in the liver and multiple other tissues, and are partially growth hormone dependent. These peptides interact with specific high affinity receptors, designated as type I and type II IGF receptors, as well as with the insulin receptor. IGFs have direct effects on somatic growth and on the proliferation of many tissues and cell types, both in vivo and in vitro. IGF-I is currently thought to be the main mediator of the growth promoting actions of human growth hormone and IGFs also have a profound effect on carbohydrate and lipid metabolism, distinct from that of insulin. A recently recognized class of proteins which have high affinity and specificity for the IGFs, the IGF binding proteins (designated as IG...

Insulin-like growth factors (IGFs): implications for aging.

The insulin-like growth factors (IGF)-I and IGF-II are peptides with structural homology to insulin and potent mitogenic and anabolic actions in vitro and in vivo. IGF-I levels are growth hormone (GH)-dependent and vary strikingly with age. IGF-I levels are typically low in infancy and childhood, increase dramatically during puberty, and then gradually decline with advancing age. Whether age-associated changes in GH production or sex steroid secretion, or other unknown factors, cause diminished IGF production in the elderly remains to be determined. In the brain, IGF-II appears to be the most prevalent IGF, but a truncated form of IGF-I also has been recognized. IGF actions are mediated by binding to a family of receptors, which includes the insulin receptor, the structurally homologous type I IGF receptor, and the IGF-II/M-6P receptor, all of which are found in the central nervous system. Additionally, the IGFs bind with high affinity to a family of IGF-binding proteins (IGFBPs). Of the six known IGFBPs, IGFBP-2 appears to be the major one in the mammalian brain and is a major component of CSF. Immunoreactive IGFBP-2 has been identified in astrocytes, and its mRNA has been identified in fetal and adult brain and choroid plexus. The IGFBPs transport the IGFs in serum and other body fluids and appear to regulate IGF access to receptors. In vivo regulation of IGFBPs includes tissue-specific proteases, which cleave specific IGFBPs, altering their affinities for IGF peptides.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin-like growth factor-II (IGF-II) and IGF binding proteins in human endometrium

The insulin-like growth factor autocrine/paracrine system is believed to play a role in steroid-mediated endometrial differentiation. It is constituted of the mitogenic peptides (IGF-I and IGF-II), membrane receptors, and a family of high-affinity binding proteins (IGFBPs) that regulate the actions of the IGFs at their target cells. We have investigated expression of the mRNAs encoding the three major IGFBPs (IGFBP-1, IGFBP-2, and IGFBP-3) in human endometrium and have found, by Northern analysis, differential expression of all three mRNAs in secretory compared to proliferative endometrium, different steroidal milieux. IGF-II mRNAs were also detected in secretory endometrium. Finally, we found that human endometrial stromal cells in culture synthesize and secrete IGFBP-2 and IGFBP-3, and that the synthesis of IGFBP-2 is regulated by steroid hormones.