Bercu B B, Root A W, Shulman D I
J Clin Endocrinol Metab. 1986 Oct;63(4):968-73. doi: 10.1210/jcem-63-4-968.
The integrity of dopaminergic and alpha-adrenergic neurotransmitter regulation of GH secretion was examined in children with decreased GH secretion. Children with GH neurosecretory dysfunction (GHND; n = 16) those with classical GH deficiency (n = 9), and short but otherwise normal children (n = 12) underwent 24 h GH studies (blood sampling every 20 min for 24 h) and provocative tests using arginine, insulin hypoglycemia, L-dopa (dopaminergic) and clonidine (alpha-adrenergic), and GH-releasing hormone (GHRH). GHND was defined as children with height in the first percentile or below, growth velocity of 4 cm/yr or less, low plasma somatomedin-C for age, delayed skeletal age by 2 or more yr, peak serum GH responses to any one (or more) provocative test of 10 ng/ml or more, and mean 24-h GH concentration below 3 ng/ml. GHND and GH-deficient children had reduced endogenous GH secretion, expressed as mean serum 24-h GH concentration [1.6 +/- 0.1 (+/- SEM) and 2.1 +/- 0.1 vs. 6.1 +/- 0.5 ng/ml (GH-deficient and GHND vs. normal, respectively); P less than 0.01]. the mean peak serum GH levels after arginine [8.2 +/- 2.0 vs. 20.8 +/- 6.6 ng/ml (GHND vs. normal); P less than 0.05] and insulin [9.3 +/- 1.0 vs. 16.2 +/- 1.7 ng/ml (GHND vs. normal); P less than 0.01) were lower in GHND children. The mean peak responses after L-dopa [13.4 +/- 3.4 vs. 14.6 +/- 4.7 ng/ml (GHND vs. normal); P = NS] and clonidine [19.0 +/- 2.2 vs. 23.3 +/- 3.8 ng/ml (GHND vs. normal); P = NS] were preserved in GHND children. In GH-deficient children, mean peak serum GH concentrations after all four provocative tests were low (arginine, 2.7 +/- 0.8; insulin, 2.6 +/- 0.8; L-dopa, 3.0 +/- 0.9; clonidine, 3.4 +/- 1.0 ng/ml; all P less than 0.01 vs. normal). The mean peak serum GH concentration after GHRH was blunted in GH-deficient children (9.1 +/- 1.7 ng/ml) compared to those in GHND (32.9 +/- 8.5 ng/ml) and normal (43.2 +/- 6.4 ng/ml) children (P less than 0.01). The area under the GH curve after GHRH stimulation was greater for normal than GHND children (P less than 0.05). These data demonstrate preservation of dopaminergic and alpha-adrenergic neurotransmitter pathways in GHND children. They further suggest a defect in the release of pituitary GH secondary to an abnormality in alternative neurotransmitter pathways resulting in decreased GHRH and/or increased somatostatin secretion.
对生长激素（GH）分泌减少的儿童，研究了多巴胺能和α-肾上腺素能神经递质对GH分泌调节的完整性。对生长激素神经分泌功能障碍（GHND；n = 16）、典型生长激素缺乏症（n = 9）以及身材矮小但其他方面正常的儿童（n = 12）进行了24小时GH研究（每20分钟采血一次，共24小时），并使用精氨酸、胰岛素低血糖、左旋多巴（多巴胺能）、可乐定（α-肾上腺素能）和生长激素释放激素（GHRH）进行激发试验。GHND定义为身高处于第一百分位数或更低、生长速度每年4厘米或更低、按年龄计算血浆生长调节素-C水平低、骨骼年龄延迟2年或更长、对任何一项（或多项）激发试验的血清GH峰值反应为10 ng/ml或更高，且24小时GH平均浓度低于3 ng/ml的儿童。GHND和生长激素缺乏症儿童的内源性GH分泌减少，以血清24小时GH平均浓度表示[分别为1.6±0.1（±标准误）和2.1±0.1，而正常儿童为6.1±0.5 ng/ml（生长激素缺乏症和GHND儿童与正常儿童相比）；P＜0.01]。GHND儿童精氨酸刺激后血清GH平均峰值水平[8.2±2.0与20.8±6.6 ng/ml（GHND与正常儿童相比）；P＜0.05]和胰岛素刺激后[9.3±1.0与16.2±1.7 ng/ml（GHND与正常儿童相比）；P＜0.01]较低。GHND儿童左旋多巴刺激后平均峰值反应[13.4±3.4与14.6±4.7 ng/ml（GHND与正常儿童相比）；P = 无显著差异]和可乐定刺激后[19.0±2.2与23.3±3.8 ng/ml（GHND与正常儿童相比）；P = 无显著差异]得以保留。在生长激素缺乏症儿童中，所有四项激发试验后血清GH平均峰值浓度均较低（精氨酸，2.7±0.8；胰岛素，2.6±0.8；左旋多巴，3.0±0.9；可乐定，3.4±1.0 ng/ml；与正常儿童相比，所有P＜0.01）。与GHND儿童（32.9±8.5 ng/ml）和正常儿童（43.2±6.4 ng/ml）相比，生长激素缺乏症儿童GHRH刺激后血清GH平均峰值浓度降低（9.1±1.7 ng/ml）（P＜0.01）。GHRH刺激后GH曲线下面积正常儿童大于GHND儿童（P＜0.05）。这些数据表明GHND儿童中多巴胺能和α-肾上腺素能神经递质途径得以保留。它们进一步提示，由于替代神经递质途径异常导致垂体GH释放缺陷，从而导致GHRH分泌减少和/或生长抑素分泌增加。
