Guevara-Aguirre Jaime, Bright George M, Guevara Alexandra, Tite Maria, Saavedra Jannette, Teran Enrique, Rosenfeld Ron G
Colegio de Ciencias de la Salud, Universidad San Francisco de Quito USFQ, Quito, Pichincha 170901, Ecuador.
Instituto de Endocrinología (IEMYR), Quito, Pichincha 170517, Ecuador.
J Clin Endocrinol Metab. 2025 Jul 15;110(8):e2640-e2646. doi: 10.1210/clinem/dgae835.
Body proportions are the objective parameters of harmonious growth and reflect the interplay of genetic, environmental, metabolic, and hormonal actions. Mutations in the growth hormone receptor gene (GHR) result in severe growth failure. The study of individuals affected with these mutations can inform us about the role of growth peptides in harmonious, proportional growth.
The aim of this study was to critically assess the role of the growth hormone-insulin-like growth factor (GH-IGF) axis in statural growth and in particular body proportionality.
In this epidemiological, noninterventional study, we compared the anthropometric measurements and body proportions of an Ecuadorian cohort of adults with GH insensitivity (GHI) due to a homozygous mutation at codon 180/exon 6 of GHR, to their carrier and noncarrier relatives, and to noncarrier unrelated controls. We also investigated the relations between serum IGF-I concentrations and auxological determinations.
In this cohort of 201 adults, sex-specific distributions of height (Ht), lower segment, upper segment, arm span, head circumference (HC), and hand and foot length were lower in the GHI individuals than in the other groups. The GHI individuals had the lowest lower segment/Ht, the highest upper segment/Ht, the lowest arm span/Ht and the highest HC/Ht ratio. Hand and foot length/Ht ratios were not uniformly affected. Serum IGF-I concentrations displayed a positive logarithmic correlation with all body measurements but were negatively correlated with the HC/Ht ratio.
These findings indicate that individuals homozygous for the GHR mutation have disharmonious body proportions due to abnormal GH/IGF-I action on the growth of the long bones. Contrary to common assumptions, disruption of the GH-IGF axis results in disproportionality and disharmonious growth.
身体比例是和谐生长的客观参数，反映了遗传、环境、代谢和激素作用之间的相互影响。生长激素受体基因（GHR）突变会导致严重的生长发育迟缓。对受这些突变影响的个体进行研究，有助于我们了解生长肽在和谐、成比例生长中的作用。
本研究的目的是严格评估生长激素 - 胰岛素样生长因子（GH - IGF）轴在身高增长，尤其是身体比例方面的作用。
在这项流行病学非干预性研究中，我们比较了因GHR第180位密码子/外显子6纯合突变而导致生长激素不敏感（GHI）的厄瓜多尔成年人群体的人体测量数据和身体比例，将其与他们的携带者和非携带者亲属，以及非携带者非亲属对照进行比较。我们还研究了血清IGF - I浓度与人体测量学测定之间的关系。
在这201名成年人队列中，GHI个体的身高（Ht）、下肢、上肢、臂展、头围（HC）以及手足长度的性别特异性分布低于其他组。GHI个体的下肢/Ht比值最低，上肢/Ht比值最高，臂展/Ht比值最低，HC/Ht比值最高。手足长度/Ht比值并非均一受到影响。血清IGF - I浓度与所有身体测量值呈正对数相关，但与HC/Ht比值呈负相关。
这些发现表明，GHR突变纯合个体由于GH/IGF - I对长骨生长的异常作用而导致身体比例不协调。与通常的假设相反，GH - IGF轴的破坏会导致比例失调和生长不协调。
