Carmignac D F, Wells T, Carlsson L M, Clark R G, Robinson I C
Division of Neurophysiology and Neuropharmacology, National Institute for Medical Research, Mill Hill, London, U.K.
J Endocrinol. 1992 Dec;135(3):447-57. doi: 10.1677/joe.0.1350447.
There are GH-binding proteins (GHBPs) present in the blood of many species, and these correspond to the extracellular GH-binding domain of the GH receptor. In the rat, GHBP arises by alternative splicing of the GH receptor mRNA, but little is known of the physiological role of circulating GHBP, or its relationship with episodic GH secretion. We have developed a sensitive radioimmunoassay based on recombinant GHBP, and have measured rat GHBP levels in small samples of plasma from normal and GH-deficient dwarf rats. In normal adult rats, GHBP levels were two- to threefold higher in females than in males (16.6 +/- 0.8 vs 6.4 +/- 0.4 micrograms/l, P < 0.001), but this sex difference was not seen in dwarf rats. A continuous infusion of human GH in dwarf males raised plasma GHBP to 23.5 +/- 3.5 micrograms/l compared with 6.7 +/- 0.5 micrograms/l in sham-infused animals, whereas suppression of GH by continuous infusion of a long-acting somatostatin analogue in female dwarf rats had no effect on GHBP. In anaesthetized rats, large changes in plasma GH caused by i.v. administration of rat GH, somatostatin or GH-releasing factor did not affect GHBP acutely. Both GH and GHBP were also measured in serial blood samples from conscious normal and dwarf rats. A sexually dimorphic GH secretory pattern was observed in both strains. Males showed peaks and troughs of GH every 3 h varying over a 100-fold range, whereas females exhibited more continuous GH secretion. Despite the large fluctuations in endogenous GH, GHBP levels remained relatively constant in individual normal or dwarf males, as well as in females of both strains, and there was no significant correlation between GH and GHBP either in individual rats or as a group. Our results suggest that GHBP is GH-dependent in the longer term, and that the higher GHBP levels in female rats require their continuous GH secretory pattern. However, plasma GHBP levels remain stable and are not affected by acute changes in endogenous or exogenous GH.
许多物种的血液中都存在生长激素结合蛋白（GHBP），这些蛋白与生长激素受体的细胞外生长激素结合结构域相对应。在大鼠中，GHBP是由生长激素受体mRNA的可变剪接产生的，但关于循环中GHBP的生理作用及其与生长激素脉冲式分泌的关系却知之甚少。我们基于重组GHBP开发了一种灵敏的放射免疫测定法，并测量了正常和生长激素缺乏型侏儒大鼠少量血浆样本中的大鼠GHBP水平。在正常成年大鼠中，雌性的GHBP水平比雄性高两到三倍（16.6±0.8对6.4±0.4微克/升，P<0.001），但在侏儒大鼠中未观察到这种性别差异。给侏儒雄性大鼠持续输注人生长激素，使血浆GHBP升高至23.5±3.5微克/升，而假输注动物为6.7±0.5微克/升，而给雌性侏儒大鼠持续输注长效生长抑素类似物抑制生长激素对GHBP没有影响。在麻醉的大鼠中，静脉注射大鼠生长激素、生长抑素或生长激素释放因子引起的血浆生长激素的大幅变化并未急性影响GHBP。还对清醒的正常和侏儒大鼠的系列血样进行了生长激素和GHBP的测定。在两个品系中均观察到了性别差异的生长激素分泌模式。雄性大鼠每3小时出现一次生长激素的峰值和谷值，变化范围超过100倍，而雌性大鼠的生长激素分泌则较为持续。尽管内源性生长激素有很大波动，但在个体正常或侏儒雄性大鼠以及两个品系的雌性大鼠中，GHBP水平保持相对恒定，并且在个体大鼠或作为一个群体中，生长激素与GHBP之间均无显著相关性。我们的结果表明，从长期来看，GHBP依赖于生长激素，雌性大鼠中较高的GHBP水平需要其持续的生长激素分泌模式。然而，血浆GHBP水平保持稳定，不受内源性或外源性生长激素急性变化的影响。
