Skeletal Growth Acceleration with Growth Hormone Secretagogues in Transgenic Growth Retarded Rats: Pattern‐Dependent Effects and Mechanisms of Desensitization
Skeletal Growth Acceleration with Growth Hormone Secretagogues in Transgenic Growth Retarded Rats: Pattern‐Dependent Effects and Mechanisms of Desensitization
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转基因生长迟缓大鼠中生长激素促分泌剂的骨骼生长加速：模式依赖性效应和脱敏机制
DOI：
10.1046/j.1365-2826.2001.00661.x
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发表时间：
2001
影响因子：
3.2
通讯作者：
P. Houston
中科院分区：
文献类型：
--
作者：
T. Wells;P. Houston
转基因生长迟缓（Tgr）大鼠是第一个生长激素（GH）缺乏症的遗传模型，外源性生长激素分泌剂（GHSs）可以促进生长。在这项研究中，我们证明了Tgr大鼠弓形核中GHS受体（GHS - R） mRNA的表达与野生型幼崽没有显著差异。我们已经证实，GHS诱导的体重增加伴随着骨骼生长的加速，GHS的影响，GHRP - 6，是剂量和模式依赖的。持续输注GHRP‐6的生长反应是短暂的，同时大量注射GHRP‐6会抑制生长激素和皮质酮的反应。这种脱敏没有弓形GHS‐R mRNA表达下调，但伴随着心室周围生长抑素mRNA表达升高。相比之下，脉冲（3小时）灌注GHRP - 6可产生持续的生长和生长激素反应，同时皮质酮反应受到抑制，弓形GH释放因子（GRF） mRNA表达升高。GRF的联合输注进一步加速了骨骼生长，但垂体GH储存的显著耗竭表明这种生长速度可能不可持续。这些实验证实了Tgr大鼠在GH -缺乏性侏儒症背景下研究GHSs促进生长潜力的重要性，并表明在持续GHRP - 6治疗后，生长抑素表达升高可能介导GRF - GH和下丘脑-垂体-肾上腺轴的抑制。
The transgenic growth retarded (Tgr) rat is the first genetic model of growth hormone (GH) deficiency whose growth can be accelerated with exogenous GH secretagogues (GHSs). In this study, we have demonstrated that GHS‐receptor (GHS‐R) mRNA expression in the arcuate nucleus of Tgr rats was not significantly different to that in wild‐type littermates. We have confirmed that GHS‐induced elevation in body weight gain was accompanied by acceleration of skeletal growth, and that the effects of the GHS, GHRP‐6, were both dose‐ and pattern‐dependent. The growth response with continuous infusion of GHRP‐6 was transient, accompanied by suppression of GH and corticosterone responses to bolus injection of GHRP‐6. This desensitization occurred without downregulation of arcuate GHS‐R mRNA expression, but was accompanied by elevated periventricular somatostatin mRNA expression. In contrast, pulsatile (3‐hourly) infusion of GHRP‐6 produced sustained growth and GH responses, which were accompanied by suppression of corticosterone responses and elevated arcuate GH‐releasing factor (GRF) mRNA expression. Skeletal growth was further accelerated by coinfusion of GRF, but significant depletion of pituitary GH stores suggested that this growth rate may not be sustainable. These experiments confirm the importance of the Tgr rat for investigating the growth promoting potential of the GHSs in the context of GH‐deficient dwarfism, and suggest that elevated somatostatin expression may mediate the suppression of the GRF‐GH and hypothalamo‐pituitary‐adrenal axes following continuous GHRP‐6 treatment.
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连续输注 GH 释放肽期间生长激素 (GH) 的分泌：部分反应衰减。
DOI：
10.1210/jcem-72-6-1312
发表时间：
1991
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
DeBell,WK;Pezzoli,SS;Thorner,MO
通讯作者：
Thorner,MO
二十四小时的生长激素 (GH) 释放肽 (GHRP) 输注可增强脉动式 GH 分泌，并特别减弱对后续 GHRP 推注的反应。
DOI：
10.1210/jcem.76.5.8496311
发表时间：
1993
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
Huhn,WC;Hartman,ML;Pezzoli,SS;Thorner,MO
通讯作者：
Thorner,MO
下丘脑生长激素释放因子 (GRF) 的单克隆抗体抑制生长激素的脉冲式分泌。
影响因子：
4.8
作者：
Wehrenberg,WB;Brazeau,P;Luben,R;Bohlen,P;Guillemin,R
通讯作者：
Guillemin,R
大鼠垂体前叶膜匀浆中的生长激素释放因子结合位点：糖皮质激素的调节。
影响因子：
4.8
作者：
Seifert,H;Perrin,M;Rivier,J;Vale,W
通讯作者：
Vale,W