Mannor D A, Winer L M, Shaw M A, Baumann G
Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611.
J Clin Endocrinol Metab. 1991 Jul;73(1):30-4. doi: 10.1210/jcem-73-1-30.
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.
生长激素结合蛋白（GH-BP）最近在人血浆中被发现，但其生物学功能尚不清楚。高亲和力GH-BP与生长激素受体相关，可能调节生长激素与组织受体的相互作用，而低亲和力GH-BP在这方面可能是无活性的。受体结合的调节可能导致生长激素生物活性的调节。为了解决这些问题，我们研究了纯化的GH-BP以及全血浆对生长激素与人、兔和雌性大鼠肝脏及大鼠脂肪细胞中受体结合的影响。高亲和力BP以剂量依赖性方式抑制生长激素与受体的结合。在BP浓度的生理范围内观察到了显著的抑制作用；在这方面，人肝脏和大鼠脂肪细胞最为敏感。相比之下，低亲和力BP对生长激素的受体结合没有影响。人全血浆也抑制生长激素与受体的结合。这种作用可归因于其GH-BP的含量，因为从血浆中去除或原本不存在BP会消除其抑制作用。纯化的高亲和力BP也在一定程度上抑制培养的人成纤维细胞中生长激素依赖的胰岛素样生长因子-I的产生，其程度与受体抑制相当。我们得出结论，循环中的高亲和力GH-BP通过螯合生长激素，极大地干扰了生长激素与其受体的结合，并且血浆在生长激素放射受体分析中众所周知的抑制作用很大程度上归因于这种BP。这种BP同样抑制体外培养的人成纤维细胞中的生长激素作用。
