In vitro characterization of four novel classes of growth hormone-releasing peptide.
In vitro characterization of four novel classes of growth hormone-releasing peptide.
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四类新型生长激素释放肽的体外表征。
DOI：
10.1210/endo.136.12.7588325
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发表时间：
1995
期刊：
影响因子：
4.8
通讯作者：
M J Cronin
中科院分区：
文献类型：
--
作者：
K A Elias;G S Ingle;J P Burnier;R G Hammonds;R S McDowell;T E Rawson;T C Somers;M S Stanley;M J Cronin
对六肽GH-释放肽（GHRP-6）结构/功能的重新研究导致了四类刺激GH释放的新化合物的发展。每一类表示如下：一个五肽，G-7039；四肽G-7134；假三肽G-7502；和刚性环七肽G-7203。通过大鼠垂体细胞原代培养的GH剂量反应曲线测定，这些化合物的EC50值分别为0.18、0.34、10.6和0.43 nM。为了证明这些化合物作用于假定的GHRP受体，使用包括GHRP-6和GHRH释放激素（GHRH）的组合进行挑战。所有四种新类别与GHRH联合进一步增加生长激素释放，但与GHRP-6联合不增加。暴露于新化合物45分钟后发生同源脱敏，而细胞仍对GHRH敏感。生长抑素抑制了所有这些化合物。此外，G-7039升高游离钙，与GHRP-6一样。所有四种类型的小鼠均能产生强劲的生长激素释放，PRL有少量增加，而LH、FSH、ACTH或TSH没有变化。我们得出结论，这些新化合物是垂体GH释放的有效和直接刺激物，具有通过特定的ghrp样机制介导的体外属性。
Reexamination of the hexapeptide GH-releasing peptide (GHRP-6) structure/function has lead to the development of four novel classes of compound that stimulate GH release. Each class is represented as follows: a pentapeptide, G-7039; a tetrapeptide, G-7134; a pseudotripeptide, G-7502; and a rigid cyclic heptapeptide, G-7203. The EC50 values for these compounds, determined by GH dose-response curves using primary cultures of rat pituitary cells, were 0.18, 0.34, 10.6, and 0.43 nM, respectively. To demonstrate that these compounds were acting at the putative GHRP receptor, challenges were made using combinations that included GHRP-6 and GH-releasing hormone (GHRH). All four new classes further increased GH release in combination with GHRH, but not with GHRP-6. Homologous desensitization occurred after 45 min of exposure to the new compounds while the cells remained sensitive to GHRH. Somatostatin inhibited all of these compounds. Additionally, G-7039 elevated free calcium, as occurs with GHRP-6. All four classes elicited a robust GH release, a small increase in PRL, and no change in LH, FSH, ACTH, or TSH. We conclude that these novel compounds are potent and direct stimulators of pituitary GH release, with in vitro attributes that suggest mediation via a specific GHRP-like mechanism.
口服生长激素 (GH) 释放肽可刺激正常男性的 GH 分泌。
DOI：
10.1210/jcem.74.6.1592884
发表时间：
1992
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
Hartman,ML;Farello,G;Pezzoli,SS;Thorner,MO
通讯作者：
Thorner,MO