Insulin-Like Growth Factor-1 and Growth Hormone (GH) Levels in Canine Cerebrospinal Fluid are Unaffected by GH or GH Secretagogue (MK-0677) Administration
Insulin-Like Growth Factor-1 and Growth Hormone (GH) Levels in Canine Cerebrospinal Fluid are Unaffected by GH or GH Secretagogue (MK-0677) Administration
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犬脑脊液中的胰岛素样生长因子-1 和生长激素 (GH) 水平不受 GH 或 GH 促泌剂 (MK-0677) 给药的影响
DOI：
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
M. J. V. Zwieten
中科院分区：
文献类型：
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作者：
S. Prahalada;G. Block;L. Handt;G. DeBurlet;M. Cahill;Chao;M. J. V. Zwieten
循环GH水平升高导致犬血清胰岛素样生长因子-1（IGF-1）水平呈剂量相关性升高。然而，目前尚不清楚全身IGF-1和GH水平的升高是否有助于这些激素的脑脊液（CSF）水平。因此，在犬中设计了一项研究，以确定循环GH水平升高是否是GH促分泌素（MK-0677）的结果，或者外源性GH给药是否导致犬CSF中IGF-1和GH水平升高。根据体重，将共计12只正常、年轻成年雄性犬随机分配至3个给药组（4只犬/组）。有4只溶剂对照犬。一组4只犬经口给予溶于去离子水的MK-0677（5 mg/kg/天）。第三组4只犬接受皮下注射猪GH（pGH），剂量为0.1 IU/kg/天。在开始给药前以及给药第7天和第15天，采集所有犬的血液和CSF样本。使用经验证的放射免疫分析法测定所有样本。MK-0677或pGH给药导致体重增加和血清IGF-1和GH水平增加，具有统计学显著性（P <或= 0.05）。相比之下，MK-0677给药在研究第7天或第15天未导致CSF IGF-1或GH水平显著（P > 0.05）升高。CSF IGF-1值范围为1.2 - 2.0 ng/ml，研究期间从每只犬采集的3份单独样品之间的差异极小。同样，所有犬的CSF GH水平均非常低（< 0.98 ng/ml至2.4 ng/ml），与给药组无关。这项研究表明，IGF-1或GH的循环水平与正常犬CSF中这些激素的水平之间没有相关性。溶剂对照犬的血清和CSF IGF-1水平之间的差异约为100倍，表明循环IGF-1存在血脑屏障。同样，尽管血清GH水平升高，但CSF GH水平未升高，表明正常犬中存在GH的血脑屏障。这些结果表明，犬CSF中GH和IGF-1的可能来源是CNS。
Elevation in circulating GH levels results in a dose-related increase in serum insulin-like growth factor-1 (IGF-1) levels in dogs. However, it is not known whether elevations in systemic IGF-1 and GH levels contribute to the cerebrospinal fluid (CSF) levels of these hormones. Therefore, a study was designed in dogs to determine if elevated circulating GH levels was a result of a GH secretagogue (MK-0677) or if exogenous GH administration resulted in increased IGF-1 and GH levels in the CSF of dogs. A total of 12 normal, young adult male dogs were randomized to three treatment groups (4 dogs/group) based on body weight. There were 4 vehicle control dogs. A group of 4 dogs were dosed orally with MK-0677 (5 mg/kg/day) dissolved in deionized water. A third group of 4 dogs received subcutaneous injections of porcine GH (pGH) at a dose of 0.1 IU/kg/day. From all dogs, blood and CSF samples were collected prior to the initiation of treatment and on days 7 and 15 of treatment. All samples were assayed using a validated radioimmunoassay. Administration of MK-0677 or pGH resulted in a statistically significant (P < or = 0.05) increased body weight gain and increased serum IGF-1 and GH levels. In contrast, administration of MK-0677 resulted in no significant (P > 0.05) increase in CSF IGF-1 or GH levels on days 7 or 15 of the study. The CSF IGF-1 values ranged from 1.2 to 2.0 ng/ml with minimal variation among three separate samples taken during the course of the study from each dog. Similarly, the CSF GH levels were very low (< 0.98 ng/ml to 2.4 ng/ml) in all dogs irrespective of treatment group. This study has demonstrated that there is no correlation between the circulating levels of IGF-1 or GH and the levels of these hormones in the CSF of normal dogs. An approximately 100-fold difference between serum and CSF IGF-1 levels in vehicle control dogs suggest that there is a blood-brain barrier for the circulating IGF-1. Similarly, failure to see an elevation in CSF GH levels despite increases in serum GH levels shows that there is a blood-brain barrier for GH in normal dogs. These results suggest that the likely source of GH and IGF-1 in the CSF of dogs is from the CNS.
通过每日口服 GH 促分泌素 (MK-677) 刺激健康老年受试者的生长激素 (GH)-胰岛素样生长因子 I 轴。
DOI：
10.1210/jcem.81.12.8954023
发表时间：
1996
期刊：
The Journal of clinical endocrinology and metabolism.
影响因子：
--
作者：
Chapman,IM;Bach,MA;VanCauter,E;Farmer,M;Krupa,D;Taylor,AM;Schilling,LM;Cole,KY;Skiles,EH;Pezzoli,SS;Hartman,ML;Veldhuis,JD;Gormley,GJ;Thorner,MO
通讯作者：
Thorner,MO