Maes M, Maiter D, Massa G, Ketelslegers J M
Département de Pédiatrie, Cliniques Universitaires Saint-Luc, Faculté de Médecine, Université Catholique de Louvain, Bruxelles, Belgique.
Ann Endocrinol (Paris). 1995;56(4):253-8.
In most species, the structure of the growth hormone-binding protein (GH-BP) is identical to that of the growth hormone receptor (GH-R). The affinity (Ka) of the GH-BP is however 10 x lower than that of the receptor. Two mechanisms of production of the GH-BP have been described: in the human and the rabbit, the GH-BP is cleaved near the cellular membrane by proteolysis and shed into the extracellular compartment while in murine species, the serum GH-BP is produced by alternative splicing of the gene coding for the GH receptor. The GH-BP prolongs the 1/2 life of plasma GH, dampening the free GH levels during peaks and maintaining free hormone levels during troughs via the slow dissociation of GH from the complex GH-GHBP. By controlling free GH levels within and between peaks, GH-BP would thus play an important role in modulating GH action at the cellular level. In several physiological and physiopathological conditions, GH-BP and GH-R are coordinately regulated. However, there are situations such as during pregnancy or certain periods of development where these 2 proteins are not co-expressed. Therefore, GH-BP circulating levels do not necessarily represent cellular GH-R concentrations. In the rat, GH-BP and GH-R are regulated by nutritional and endocrine factors, among those are GH, insulin and gonadal steroids. In the human, the mechanism responsible for the increase of the circulating GH-BP during infancy is still unknown. Finally, the eventual role of GH-BP in transmitting the intracellular message of GH following its binding to the receptor is still unknown.
在大多数物种中，生长激素结合蛋白（GH-BP）的结构与生长激素受体（GH-R）相同。然而，GH-BP的亲和力（Ka）比受体低10倍。已描述了GH-BP产生的两种机制：在人类和兔子中，GH-BP在细胞膜附近通过蛋白水解作用被切割并释放到细胞外区室，而在鼠类物种中，血清GH-BP是由编码GH受体的基因的可变剪接产生的。GH-BP延长了血浆GH的半衰期，通过GH与复合物GH-GHBP的缓慢解离，在峰值时降低游离GH水平，在谷值时维持游离激素水平。通过控制峰值内和峰值间的游离GH水平，GH-BP因此在调节细胞水平的GH作用中发挥重要作用。在几种生理和病理生理状况下，GH-BP和GH-R受到协同调节。然而，存在一些情况，如在怀孕期间或某些发育阶段，这两种蛋白质不共表达。因此，循环中的GH-BP水平不一定代表细胞内GH-R的浓度。在大鼠中，GH-BP和GH-R受营养和内分泌因素调节，其中包括GH、胰岛素和性腺类固醇。在人类中，婴儿期循环GH-BP增加的机制仍然未知。最后，GH-BP在GH与受体结合后传递细胞内信息的最终作用仍然未知。
