Baumann G, Vance M L, Shaw M A, Thorner M O
Department of Medicine, Northwestern Univeristy Medical School, Chicago, Illinois 60611.
J Clin Endocrinol Metab. 1990 Aug;71(2):470-3. doi: 10.1210/jcem-71-2-470.
We have previously shown that a substantial part of human GH is complexed with GH-binding proteins (BPs) when GH is incubated with plasma in vitro. The proportion of GH bound in vivo, however, is unknown and may differ because of factors that cannot be assessed in vitro, such as binding to tissue receptors, distribution of GH outside the vascular compartment, and fluctuating GH and possibly BP levels. Accordingly, we studied the plasma transport characteristics of GH in vivo in six normal men. Monomeric, natural sequence human GH (Humatrope, Eli Lilly Co.) was injected iv in a dose designed to yield physiological plasma levels. Endogenous GH was suppressed before injection with oral glucose administration. Fifteen minutes after injection, plasma was obtained and immediately analyzed by zonal and frontal analysis in gel chromatography, followed by GH measurement in the fractions by RIA. The results obtained were very similar to those derived from in vitro studies, regardless of which analytical method was used. Frontal analysis at 37 C, which most directly reflects the true bound fraction, showed that 38.8 +/- 4.7% (mean +/- SD) of GH was bound to BPs at plasma GH levels ranging from 32-59 micrograms/L, indistinguishable from in vitro results. [When allowance was made for partial BP saturation, the fraction bound at low GH levels (greater than 7 micrograms/L) was calculated as 45.5 +/- 7.5%.] There was evidence for binding to both high and low affinity BPs in the expected proportions. In contrast to complex formation between GH and BPs, no evidence was obtained for conversion of the monomeric GH to oligomeric forms. We conclude that in vitro predictions about binding of GH to BPs in human plasma are representative of in vivo conditions. Shortly after a GH pulse, almost half of plasma GH circulates in complexed form, primarily bound to the high affinity (receptor-related) BP. Aggregation of GH in plasma does not occur (at least within a 15-min period), suggesting that the pituitary is the predominant, if not sole, source of circulating GH oligomers.
我们之前已经表明，当在体外将生长激素（GH）与血浆一起孵育时，相当一部分人GH与GH结合蛋白（BP）形成复合物。然而，体内结合的GH比例尚不清楚，并且由于一些无法在体外评估的因素，其比例可能有所不同，例如与组织受体的结合、血管外腔室中GH的分布以及波动的GH水平和可能的BP水平。因此，我们研究了6名正常男性体内GH的血浆转运特征。以能产生生理血浆水平的剂量静脉注射单体、天然序列的人GH（优猛茁，礼来公司）。在注射前通过口服葡萄糖抑制内源性GH。注射后15分钟，采集血浆并立即通过凝胶色谱中的区带分析和前沿分析进行分析，随后通过放射免疫分析（RIA）测定各组分中的GH。无论使用哪种分析方法，所获得的结果与体外研究结果非常相似。37℃下的前沿分析最直接反映真实的结合部分，结果显示在血浆GH水平为32 - 59微克/升时，38.8±4.7%（平均值±标准差）的GH与BP结合，这与体外结果无差异。[当考虑到BP的部分饱和时，低GH水平（大于7微克/升）下的结合部分计算为45.5±7.5%。]有证据表明GH以预期比例与高亲和力和低亲和力BP结合。与GH和BP之间形成复合物不同，未获得单体GH转化为寡聚体形式的证据。我们得出结论，体外关于GH与人血浆中BP结合的预测代表体内情况。在GH脉冲后不久，几乎一半的血浆GH以复合形式循环，主要与高亲和力（受体相关）BP结合。血浆中GH不会发生聚集（至少在15分钟内），这表明垂体是循环GH寡聚体的主要来源（如果不是唯一来源的话）。
