Demonstration of type I and type II somatomedin receptors on bovine growth plate chondrocytes

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Abstract
The chondrocytes of the epiphyseal growth plate are the presumed target cells for hormones regulating skeletal growth. The somatomedins, a family of low molecular weight peptides, are thought to play a stimulatory role in this regulation. The cellular actions of the somatomedins are themselves determined by binding to specific receptors on target cells. Previous studies have characterized a specific receptor for somatomedin-C (Sm-C) or insulin-like growth factor I (IGF-I) on bovine growth plate chondrocytes (GPCs). We now report the characterization of a second type of somatomedin receptor on these cells that is more specific for another class of somatomedin represented by multiplication-stimulating activity (MSA) or rat insulin-like growth factor II (rIGF-II). Binding of [125I]MSA/rIGF-II to isolated GPCs was time dependent and saturable. Unlabeled Mr 7.100 MSA/rIGF-II and Sm-C/IGF-I were approximately equipotent in competing with [125I] MSA/rIGF-II for binding. while Mr 8,600 MSA/rIGF-II was an order of magnitude less potent. Low levels of competition by insulin appeared in some studies at concentrations of 10−7 M and higher. suggesting displacement of [125I]MSA/rIGF-II binding. to the Sm-C/IGF-I receptor. In affinity-labeling studies. [125I]Sm-C/IGF-I labeled a complex of Mr >300.000 (unreduced) and of Mr 140.000 (reduced). consistent with a type I somatomedin receptor composed of disulfide-linked subunits. [125I]MSA/rIGF-II labeled a Mr 240.000 moiety (unreduced) and Mr 260.000 (reduced). consistent with a type II somatomedin receptor. Both affinity-labeling and kinetic data revealed cross-binding of MSA/rIGF-II and insulin with the type I receptor and of Sm-C/IGF-I with the type II receptor. In contrast. the type II receptor did not recognize insulin. These data suggest a complex pattern of graded specificity of these receptors for their ligands. These data are consistent with the hypothesis that IGF-II as well as Sm-C/IGF-I participate in the stimulation of skeletal growth.