Falah Ghadeer, Sharvit Lital, Atzmon Gil
Faculty of Natural Sciences, University of Haifa, Haifa 3498838, Israel.
Departments of Medicine and Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Int J Mol Sci. 2023 Sep 10;24(18):13908. doi: 10.3390/ijms241813908.
Growth hormone (GH) is a peptide hormone that plays a crucial role in controlling growth, development, and lifespan. Molecular regulation of GH is accomplished via the (), which is the main factor influencing human development and is essential to optimal functioning of the GH/IGF-I axis. Two GHR isoforms have been studied, according to the presence (flGHR) or absence (d3GHR) of exon 3. The d3GHR isoform, which lacks exon 3 has recently been related to longevity; individuals carrying this isoform have higher receptor activity, improved signal transduction, and alterations in the treatment response and efficacy compared with those carrying the wild type (WT) isoform (flGHR). Further, studies performed in patients with acromegaly, Prader-Willi syndrome, Turner syndrome, small for gestational age (SGA), and growth hormone deficiency (GHD) suggested that the d3GHR isoform may have an impact on the relationship between GH and IGF-I levels, height, weight, BMI, and other variables. Other research, however, revealed inconsistent results, which might have been caused by confounding factors, including limited sample sizes and different experimental methods. In this review, we lay out the complexity of the GHR isoforms and provide an overview of the major pharmacogenetic research conducted on this ongoing and unresolved subject.
生长激素（GH）是一种肽类激素，在控制生长、发育和寿命方面起着至关重要的作用。生长激素的分子调节是通过（）完成的，（）是影响人类发育的主要因素，对生长激素/胰岛素样生长因子-I（GH/IGF-I）轴的最佳功能至关重要。根据外显子3的存在（全长生长激素受体，flGHR）或缺失（d3GHR），已经研究了两种生长激素受体（GHR）亚型。缺乏外显子3的d3GHR亚型最近与长寿有关；与携带野生型（WT）亚型（flGHR）的个体相比，携带这种亚型的个体具有更高的受体活性、改善的信号转导，以及治疗反应和疗效的改变。此外，对肢端肥大症、普拉德-威利综合征、特纳综合征、小于胎龄儿（SGA）和生长激素缺乏症（GHD）患者进行的研究表明，d3GHR亚型可能会影响生长激素与胰岛素样生长因子-I水平、身高、体重、体重指数（BMI）及其他变量之间的关系。然而，其他研究得出了不一致的结果，这可能是由混杂因素引起的，包括样本量有限和实验方法不同。在这篇综述中，我们阐述了生长激素受体亚型的复杂性，并概述了在这个仍在进行且尚未解决的主题上进行的主要药物遗传学研究。
