Takahashi Y, Chihara K
Third Division, Department of Medicine, Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650, Japan.
Int J Mol Med. 1998 Sep;2(3):287-91. doi: 10.3892/ijmm.2.3.287.
About 80% of short children are not deficient in endogenous growth hormone (GH) and termed idiopathic short stature (ISS). The causes of impaired growth in children with ISS are various. Short stature and low insulin-like growth factor-I (IGF-I) concentration despite normal to high GH concentration suggest impaired GH effect. The prototypical GH insensitivity syndrome was described and characterized by the absent or defective GH receptors. Growth retardation resulting from biologically inactive GH was also described, but the molecular basis of biologically inactive GH has remained unclear. Recently, two unique point mutations in the GH-1 gene in the children with short stature whose GH were supposed as bioinactive were reported. Mutant GH R77C not only failed to stimulate tyrosine phosphorylation by itself, but it also inhibited the activity of wild-type GH. This mutant GH exerted an antagonistic effect. Another mutant D112G was only bio-inactive. This case was a typical Kowarski syndrome. The molecular heterogeneity of mutant GH reflected clinical phenotype of bioinactive GH syndrome.
约80%的身材矮小儿童并非内源性生长激素（GH）缺乏，被称为特发性身材矮小（ISS）。ISS患儿生长受损的原因多种多样。尽管GH浓度正常至高，但身材矮小且胰岛素样生长因子-I（IGF-I）浓度低提示GH作用受损。典型的GH不敏感综合征已被描述，其特征是GH受体缺失或有缺陷。也有因生物活性不高的GH导致生长发育迟缓的报道，但生物活性不高的GH的分子基础仍不清楚。最近，有报道称在身材矮小且GH被认为无生物活性的儿童中，GH-1基因存在两个独特的点突变。突变型GH R77C不仅自身不能刺激酪氨酸磷酸化，还抑制野生型GH的活性。这种突变型GH发挥了拮抗作用。另一种突变型D112G仅无生物活性。该病例为典型的科瓦尔斯基综合征。突变型GH的分子异质性反映了生物活性不高的GH综合征的临床表型。
