Regulation and action of insulin-like growth factors at the cellular level.
Present understanding of IGF-1 as a growth factor mediating integration of nutritional-hormonal interactions indicates that IGF-1 acts in both an endocrine mode on distant targets and an autocrine-paracrine mode on local targets. In the liver, the combined presence of GH, insulin, and critical metabolic fuels such as essential amino acids results in increased levels of IGF-1 messenger RNA, increased production of a high-MW IGF-1 precursor, and increased release of IGF-1 into the circulation, permitting action on distant target tissues bearing specific receptors for IGF-1. The net effect is distant amplification of anabolic hormone action via IGF-1 acting in an endocrine mode. In extrahepatic tissues, both 'general' anabolic hormones (insulin and GH) as well as 'specific' hormones (e.g. gonadotropins) acting on a wide variety of targets (including fibroblasts and chondrocytes as well as granulosa and Leydig cells) promote both local secretion of IGF-1 and an increase in IGF-1 receptors. Local actions of IGF-1 then result in a secondary increase in both hormone receptors and hormone responses. The net effect is local amplification of hormone action via IGF-1 acting as a growth factor in an autocrine-paracrine mode.
Phillips
L S
LS
Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30303.
Harp
J B
JB
Goldstein
S
S
Klein
J
J
Pao
C I
CI
D000818:Animals; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D011956:Receptors, Cell Surface / Q000378:metabolism; D017451:Receptors, Somatomedin; D013002:Somatomedins / Q000235:genetics / Q000502:physiology*
D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I