Binding of intact and cleaved human growth hormone to hepatic receptors and plasma binding proteins.
The binding of intact (i) and cleaved (c) 125I-labeled human GH to the hepatic GH-binding sites and to the plasma GH-binding protein (GH-BP) of rabbits was compared. The c-hGH label was prepared by incubation of the iodinated hormone with the plasmalemal fraction of pregnant rat liver. Unlabeled c-hGH was prepared in milligram quantities by digestion with plasmin. The c-hGH label revealed both high and low affinity binding sites on the rabbit liver membranes when it was displaced by unlabeled c-hGH. Cleavage of the hGH label caused a substantial decrease in its affinity for the low affinity site. When i-hGH was used to displace either i-hGH or c-hGH tracers, it failed to discriminate between the two classes of binding sites, as it had equally high affinity for both. The c-hGH had a substantilly lower affinity for the plasma GH-BP than did the i-hGH. This difference is consistent with the c-hGH having an increased bioactivity, but not with its reported slow clearance rate. If cleavage of GH occurs at its sites of action, the lowered affinity for the plasma GH-BP, with retention of high affinity for the high affinity site, could increase its potency relative to that of the i-hGH.
Ingram
R T
RT
Department of Integrative Biology, University of California, Berkeley 94720.
Afshari
N
N
Nicoll
C S
CS
D000818:Animals; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000097:blood*; D002462:Cell Membrane / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005341:Fibrinolysin; D013006:Growth Hormone / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism; D008970:Molecular Weight; D010446:Peptide Fragments / Q000302:isolation & purification / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D011986:Receptors, Somatotropin / Q000378:metabolism*
D002352:Carrier Proteins; D010446:Peptide Fragments; D011986:Receptors, Somatotropin; D013006:Growth Hormone; D005341:Fibrinolysin; C051815:somatotropin-binding protein