title: Demonstration of type I and type II somatomedin receptors on bovine growth plate chondrocytes.
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]MSA/rIGF-I labeled a complex of Mr greater than 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.
authors.affiliation: Department of Orthopaedics, Massachusetts General Hospital, Boston 02114.
authors.forename: S B
authors.initials: SB
authors.lastname: Trippel
authors.forename: S D
authors.initials: SD
authors.lastname: Chernausek
authors.forename: J J
authors.initials: JJ
authors.lastname: Van Wyk
authors.forename: A C
authors.initials: AC
authors.lastname: Moses
authors.forename: H J
authors.initials: HJ
authors.lastname: Mankin
mesh_terms: D000345:Affinity Labels / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D002356:Cartilage / Q000166:cytology / Q000648:ultrastructure; D002417:Cattle; D004591:Electrophoresis, Polyacrylamide Gel; D006132:Growth Plate / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D007457:Iodine Radioisotopes; D011972:Receptor, Insulin / Q000032:analysis* / Q000378:metabolism; D017451:Receptors, Somatomedin
chemical_list: D000345:Affinity Labels; D007457:Iodine Radioisotopes; D017451:Receptors, Somatomedin; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D011972:Receptor, Insulin