Molecular cloning and expression of a human anterior pituitary receptor for growth hormone-releasing hormone.

Molecular cloning and expression of a human anterior pituitary receptor for growth hormone-releasing hormone.
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DOI:
10.1210/mend.7.1.7680413
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发表时间:
1993
影响因子:
--
通讯作者:
B. Gaylinn;J. Harrison;J. Zysk;C. Lyons;K. Lynch;M. Thorner
B. Gaylinn;J. Harrison;J. Zysk;C. Lyons;K. Lynch;M. Thorner
中科院分区:
医学2区
文献类型:
--
作者:
B. Gaylinn;J. Harrison;J. Zysk;C. Lyons;K. Lynch;M. Thorner

文献摘要

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生长激素释放激素(GHRH)通过GHRH受体(GHRH-R)发挥作用,在垂体生长激素合成和分泌的调节中起关键作用。GHRH可能在其他组织中发挥其他作用。在这里,我们报告的cDNA编码人GHRH-R的克隆从肢端肥大症垂体cDNA文库。分离的cDNA编码一个423个氨基酸的蛋白质,具有7个推定的跨膜结构域特征的G蛋白偶联受体。它是G蛋白偶联受体促胰液素家族的成员,与血管活性肠肽、促胰液素、降钙素和PTH的受体分别具有47%、42%、35%和28%的同一性。在COS细胞中瞬时表达该cDNA诱导饱和,高亲和力,GHRH特异性结合,也刺激细胞内cAMP积累响应于生理浓度的GHRH。一个特定的GHRH拮抗剂阻断结合和第二信使反应。北方分析表明,GHRH-R mRNA在垂体提取物中含量最高,在其它组织中未检测到。
GH-releasing hormone (GHRH), acting through the GHRH receptor (GHRH-R), plays a pivotal role in the regulation of GH synthesis and secretion in the pituitary. It is possible that GHRH may serve other roles in other tissues. Here we report the cloning of a cDNA encoding a human GHRH-R from an acromegalic pituitary cDNA library. The isolated cDNA encodes a 423-amino acid protein that has seven putative transmembrane domains characteristic of G-protein-coupled receptors. It is a member of the secretin family of G-protein-coupled receptors and has 47%, 42%, 35%, and 28% identity with receptors for vasoactive intestinal peptide, secretin, calcitonin, and PTH, respectively. Transient expression of this cDNA in COS cells induced saturable, high affinity, GHRH-specific binding and also stimulated intracellular cAMP accumulation in response to physiological concentrations of GHRH. A specific GHRH antagonist blocked both binding and second messenger response. Northern analysis indicated that GHRH-R mRNA was most abundant in extracts of pituitary and was not detected in other tissues.