PLASMA GROWTH-HORMONE (GH)-BINDING PROTEINS - EFFECT ON GH BINDING TO RECEPTORS AND GH ACTION

GH-binding proteins (GH-BP) have recently been discovered in human plasma, but their biological function is unknown. The high affinity GH-BP is related to the GH receptor and may modulate the interaction of GH with tissue receptors, whereas the low affinity GH-BP should be inert in this regard. Modulation of receptor binding probably results in modulation of GH bioactivity. To address these issues, we examined the effects of purified GH-BPs as well as whole plasma on GH binding to receptors in human, rabbit, and female rat liver and in rat adipocytes. High affinity BP inhibited binding of GH to receptors in a dose-dependent fashion. Substantial inhibition was observed within the physiological range of BP concentrations; human liver and rat adipocytes were the most sensitive in this regard. In contrast, the low affinity BP had no effect on receptor binding of GH. Whole human plasma also inhibited GH binding to receptors. This effect could be attributed to its content of GH-BP, since removal or primary absence of the BP from plasma abolished its inhibitory effect. Purified high affinity BP also inhibited GH-dependent insulin-like growth factor-I production by cultured human fibroblasts to a degree comparable to receptor inhibition. We conclude that the circulating high affinity GH-BP, by sequestering GH, substantially interferes with binding of GH to its receptor, and that the well known inhibitory effect of plasma in RRAs for GH is largely due to this BP. GH action in human fibroblasts in vitro is similarly inhibited by this BP.