Binding of intact and cleaved human growth hormone to hepatic receptors and plasma binding proteins

Abstract

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.