An Early Reduction in GH Peak Amplitude in Preproghrelin-Deficient Male Mice Has a Minor Impact on Linear Growth
An Early Reduction in GH Peak Amplitude in Preproghrelin-Deficient Male Mice Has a Minor Impact on Linear Growth
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DOI：
10.1210/en.2014-1126
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发表时间：
2014-09-01
期刊：
影响因子：
4.8
通讯作者：
Tolle, Virginie
中科院分区：
文献类型：
--
作者：
Hassouna, Rim;Zizzari, Philippe;Tolle, Virginie
Ghrelin是由作为GH促分泌素受体1a的内源性配体的proghrelin肽加工而成的肠道激素。内源性生长激素释放肽对生长激素脉冲式分泌和线性生长的调节作用有待进一步研究。本研究的目的是描绘内源性行动preproghrelin外周和中央组成部分的GH轴。因此，GH分泌的超日型测定在年轻和老年preproghrelin缺乏男性。在6小时内每10分钟通过尾部放血收集血样。通过去卷积分析GH脉动模式表明，GH在所有基因型中以超日方式分泌，主要分泌峰发生在约3小时的间隔。在老年小鼠中，与年轻动物相比，峰值数量减少，分泌不太不规则。值得注意的是，在年轻的Ghrl（-/-）小鼠中，GH分泌爆发的幅度显著降低。然而，在年龄较大的小鼠中，基因型差异不太显著。年轻的Ghrl（-/-）小鼠GH脉动性的变化与GH垂体含量和血浆IGF-I浓度降低的趋势相关，但对线性生长的影响很小。在Ghrl（+/-）小鼠中，尽管酰基生长素释放肽与去酰基生长素释放肽的比率降低，但GH分泌未受损。Ghrelin缺乏与下丘脑GHRH含量减少或对GHRH刺激反应改变无关。因此，GHRH产生和/或敏感性的降低并不能主要解释年轻Ghrl（-/-）小鼠GH脉冲式分泌的改变。相反，GHRH表达在年轻而非年老的Ghrl（-/-）小鼠中升高，表明内源性生长激素释放肽的缺乏导致的差异性代偿反应根据年龄发生。这些结果表明，内源性生长激素释放肽是生长中小鼠GH脉冲幅度的调节剂，但不显著调节线性生长。
Ghrelin is a gut hormone processed from the proghrelin peptide acting as the endogenous ligand of the GH secretagogue receptor 1a. The regulatory role of endogenous ghrelin on pulsatile GH secretion and linear growth had to be established. The aim of the present study was to delineate the endogenous actions of preproghrelin on peripheral and central components of the GH axis. Accordingly, the ultradian pattern of GH secretion was measured in young and old preproghrelin-deficient males. Blood samples were collected by tail bleeding every 10 minutes over a period of 6 hours. Analysis of the GH pulsatile pattern by deconvolution showed that GH was secreted in an ultradian manner in all genotypes, with major secretory peaks occurring at about 3-hour intervals. In older mice, the peak number was reduced and secretion was less irregular compared with younger animals. Remarkably, in young Ghrl(-/-) mice, the amplitude of GH secretory bursts was significantly reduced. In older mice, however, genotype differences were less significant. Changes in GH pulsatility in young Ghrl(-/-) mice were associated with a tendency for reduced GH pituitary contents and plasma IGF-I concentrations, but with only a minor impact on linear growth. In Ghrl(+/-) mice, despite reduced Acyl ghrelin to des-acyl ghrelin ratio, GH secretion was not impaired. Ghrelin deficiency was not associated with a reduction in hypothalamic GHRH content or altered response to GHRH stimulation. Therefore, reduction in GHRH production and/or sensitivity do not primarily account for the altered GH pulsatile secretion of young Ghrl(-/-) mice. Instead, GHRH expression was elevated in young but not old Ghrl(-/-) mice, suggesting that differential compensatory responses resulting from the absence of endogenous ghrelin is occurring according to age. These results show that endogenous ghrelin is a regulator of GH pulse amplitude in growing mice but does not significantly modulate linear growth.