Dávila Norma, Shea Brian T, Omoto Keiichi, Mercado Moises, Misawa Shogo, Baumann Gerhard
Department of Medicine, Northwestern University Medical School and Veterans Administration Chicago Health Care System, IL 60611, USA.
J Pediatr Endocrinol Metab. 2002 Mar;15(3):269-76. doi: 10.1515/jpem.2002.15.3.269.
The molecular basis and biochemical mediators of genetic growth propensity and adult height achievement in the general population are largely unknown. Pygmies represent one extreme of the height spectrum that may provide important clues regarding this issue. Previous studies in pygmies from Africa and Papua-New Guinea have shown decreased serum levels of growth hormone binding protein (GHBP), the circulating ectodomain of the growth hormone receptor (GHR). By inference, a similar limitation in tissue GHR expression has been assumed to be responsible for the partial growth hormone (GH) resistance observed in African pygmies. It is not clear how generalizable this concept is to other populations. To address this question, we studied two pygmy populations from the Philippines (Aeta and Mamanwa people) that are unrelated to the African pygmies. Serum GHBP and IGF-I levels were significantly decreased in both pygmy populations, compared to normal-statured Philippino controls. The results, together with previous observations in African and New Guinean pygmies, indicate that short stature is associated with low serum GHBP levels in pygmy populations of diverse origins and in different parts of the world. This strengthens the tentative postulate that the GHBP/GHR system plays an important role in the genetic and perhaps nutritional determination of adult stature in humans. Molecular genetic studies of the GHR gene in various pygmy populations may shed further light on the mystery of pygmy short stature.
一般人群中遗传生长倾向和成年身高的分子基础及生化介质在很大程度上尚不清楚。俾格米人代表了身高范围的一个极端，这可能为该问题提供重要线索。此前对来自非洲和巴布亚新几内亚的俾格米人的研究表明，生长激素结合蛋白（GHBP）的血清水平降低，GHBP是生长激素受体（GHR）的循环胞外域。由此推断，组织GHR表达的类似限制被认为是非洲俾格米人观察到的部分生长激素（GH）抵抗的原因。目前尚不清楚这一概念对其他人群的普遍适用性如何。为了解决这个问题，我们研究了来自菲律宾的两个与非洲俾格米人无关的俾格米人群体（阿埃塔人和马曼瓦人）。与身材正常的菲律宾对照组相比，两个俾格米人群体的血清GHBP和IGF-I水平均显著降低。这些结果与之前对非洲和新几内亚俾格米人的观察结果一起表明，身材矮小与不同起源和世界不同地区的俾格米人群体中血清GHBP水平低有关。这强化了一个初步假设，即GHBP/GHR系统在人类成年身高的遗传以及可能的营养决定中起重要作用。对各种俾格米人群体的GHR基因进行分子遗传学研究可能会进一步揭示俾格米人身材矮小的奥秘。
