Growth hormone deficiency in pseudohypoparathyroidism type 1a: Another manifestation of multihormone resistance
Growth hormone deficiency in pseudohypoparathyroidism type 1a: Another manifestation of multihormone resistance
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DOI：
10.1210/jc.2003-030028
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发表时间：
2003-09-01
影响因子：
5.8
通讯作者：
Levine, MA
中科院分区：
文献类型：
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作者：
Germain-Lee, EL;Groman, J;Levine, MA
奥尔布赖特遗传性骨营养不良症（AHO）是一种由编码G(s) α链的基因GNAS1杂合失活突变引起的遗传性疾病，与身材矮小、肥胖、短指和sc骨化有关。在母系遗传等位基因上有GNAS1突变的世卫组织患者也表现出对多种激素（如甲状旁腺激素、TSH、LH、FSH）的抗性，由于父亲在特定组织中印记了半胱甲肽转录本，这种变异被称为伪性甲状旁腺功能低下（PHP） 1a型。最近的证据表明，在分泌GH的垂体生长激素中也有半胱甘肽转录本的印迹。由于这种印记可能影响生长激素依赖性刺激，我们假设母体遗传的GNAS1突变会损害生长激素的分泌。我们研究了13例1a型PHP患者的生长激素状态。9名受试者对精氨酸/左旋多巴和精氨酸/ GHRH的生长激素反应不足，他们都是肥胖且血清igf - 1浓度低。相比之下，四名gh充足的受试者都没有肥胖，而且所有人的igf - 1水平都正常。我们的数据表明，生长激素缺乏在PHP 1a型患者中很常见（69%），并可能导致who典型的肥胖和身材矮小。我们建议对所有1a型PHP患者的生长激素状态进行评估。
Albright hereditary osteodystrophy (AHO) is a genetic disorder caused by heterozygous inactivating mutations in GNAS1, the gene encoding the alpha-chain of G(s), and is associated with short stature, obesity, brachydactyly, and sc ossifications. AHO patients with GNAS1 mutations on maternally inherited alleles also manifest resistance to multiple hormones ( e. g. PTH, TSH, LH, FSH), a variant termed pseudohypoparathyroidism (PHP) type 1a, due to paternal imprinting of Galpha(s) transcripts in specific tissues. Recent evidence has shown that Galpha(s) transcripts are also imprinted in the pituitary somatotrophs that secrete GH. Because this imprinting could influence GHRH-dependent stimulation of somatotrophs, we hypothesized that maternally inherited GNAS1 mutations would impair GH secretion. We studied GH status in 13 subjects with PHP type 1a. GH responses to arginine/L-dopa and arginine/ GHRH were deficient in nine subjects, all of whom were obese and had low serum concentrations of IGF-I. By contrast, none of the four GH-sufficient subjects were obese, and all had normal IGF-I levels. Our data indicate that GH deficiency is common (69%) in PHP type 1a and may contribute to the obesity and short stature typical of AHO. We propose that GH status be evaluated in all patients with PHP type 1a.