Clayton P E, Freeth J S, Whatmore A J, Ayling R M, Norman M R, Silva C M
Endocrine Science Research Group, University of Manchester, UK.
Acta Paediatr Suppl. 1999 Feb;88(428):174-8; discussion 179. doi: 10.1111/j.1651-2227.1999.tb14382.x.
Growth hormone (GH) insensitivity is a heterogeneous condition that can result from mutations within the GH receptor (GHR) and that can be inherited as both an autosomal recessive and a dominant trait. However, evidence from a small number of growth hormone binding protein (GHBP)-positive families indicates that their GH insensitivity is independent of GHR mutations. Two of these families appear to have distinct abnormalities in GH signal transduction. Studies suggest that one family (classic Laron syndrome phenotype; designated family H) have a signalling defect close to the GHR, preventing activation of both the STAT and MAPK pathways, whereas the other family (less marked phenotype; family M) have a defect in activating MAPK but not the STAT pathway. The children studied here are specifically insensitive to GH and their defect must be exclusive to this signalling system. Thus, families with GHBP-positive GH insensitivity without GHR mutations are likely to be important models in which to study the specificity of GH signal transduction and the relationship between GH insensitive phenotype and signalling defect.
生长激素（GH）不敏感是一种异质性疾病，可由生长激素受体（GHR）内的突变引起，并且可作为常染色体隐性和显性性状遗传。然而，来自少数生长激素结合蛋白（GHBP）阳性家族的证据表明，他们的生长激素不敏感与GHR突变无关。其中两个家族在生长激素信号转导方面似乎有明显异常。研究表明，一个家族（典型的拉龙综合征表型；指定为家族H）在靠近GHR处存在信号缺陷，阻止了STAT和MAPK途径的激活，而另一个家族（表型较轻；家族M）在激活MAPK方面存在缺陷，但STAT途径未受影响。这里研究的儿童对生长激素特别不敏感，他们的缺陷必定仅限于这个信号系统。因此，没有GHR突变的GHBP阳性生长激素不敏感家族很可能是研究生长激素信号转导特异性以及生长激素不敏感表型与信号缺陷之间关系的重要模型。
