下丘脑肽生长激素释放激素（GHRH）通过结合和激活垂体型GHRH受体（GHRH-R）刺激垂体分泌生长激素（GH），后者属于七个潜在的跨膜结构域的G蛋白耦合受体家族。已经鉴定了人类肿瘤和其他垂体外组织中的GHRH-R剪接变体（SV），并对其cDNA进行了测序。剪接变体1（SV1）在所有剪接变体中与全长GHRH-R相似度最高，并通过GHRH刺激引发cAMP信号传导和丝裂原活性来保持功能。大量研究评估了GHRH激动剂和拮抗剂在内分泌学、肿瘤学、心血管学、糖尿病学、肥胖症、代谢功能障碍、老年痴呆症、眼科学、创伤愈合等领域的潜在临床应用。在本章中，我们将简要回顾GHRH-R及其SV在各种组织中的表达和潜在功能，并阐明和总结这些受体的激活、分子机制和信号通路。还讨论了GHRH类似物的治疗应用。版权所有 © 2023 Elsevier Inc. 保留所有权利。

The hypothalamic peptide growth hormone-releasing hormone (GHRH) stimulates the secretion of growth hormone (GH) from the pituitary through binding and activation of the pituitary type of GHRH receptor (GHRH-R), which belongs to the family of G protein-coupled receptors with seven potential membrane-spanning domains. Splice variants of GHRH-Rs (SV) in human tumors and other extra pituitary tissues were identified and their cDNA was sequenced. Among the SVs, splice variant 1 (SV1) possesses the greatest similarity to the full-length GHRH-R and remains functional by eliciting cAMP signaling and mitogenic activity upon GHRH stimulation. A large body of work have evaluated potential clinical applications of agonists and antagonists of GHRH in diverse fields, including endocrinology, oncology, cardiology, diabetes, obesity, metabolic dysfunctions, Alzheimer's disease, ophthalmology, wound healing and other applications. In this chapter, we briefly review the expression and potential function of GHRH-Rs and their SVs in various tissues and also elucidate and summarize the activation, molecular mechanism and signalization pathways of these receptors. Therapeutic applications of GHRH analogs are also discussed.Copyright © 2023 Elsevier Inc. All rights reserved.