Growth hormone-releasing hormone and cancer.

IF 6.9 2区医学 Q1 ENDOCRINOLOGY & METABOLISM Reviews in Endocrine & Metabolic Disorders Pub Date : 2024-10-18 DOI:10.1007/s11154-024-09919-4

Iacopo Gesmundo, Francesca Pedrolli, Renzhi Cai, Wei Sha, Andrew V Schally, Riccarda Granata

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Abstract

The hypothalamic hormone growth hormone-releasing hormone (GHRH), in addition to promoting the synthesis and release of growth hormone (GH), stimulates the proliferation of human normal and malignant cells by binding to GHRH-receptor (GHRH-R) and its main splice variant, SV1. Both GHRH and GHRH-Rs are expressed in various cancers, forming a stimulatory pathway for cancer cell growth; additionally, SV1 possesses ligand independent proliferative effects. Therefore, targeting GHRH-Rs pharmacologically has been proposed for the treatment of cancer. Various classes of synthetic GHRH antagonists have been developed, endowed with strong anticancer activity in vitro and in vivo, in addition to displaying anti-inflammatory, antioxidant and immune-modulatory functions. GHRH antagonists exert indirect effects by blocking the pituitary GH/hepatic insulin-like growth factor I (IGF-I) axis, or directly inhibiting the binding of GHRH on tumor GHRH-Rs. Additionally, GHRH antagonists block the mitogenic functions of SV1 in tumor cells. This review illustrates the main findings on the antitumor effects of GHRH antagonists in experimental human cancers, along with their underlying mechanisms. The development of GHRH antagonists, with reduced toxicity and high stability, could lead to novel therapeutic agents for the treatment of cancer and inflammatory diseases.

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生长激素释放激素与癌症

下丘脑激素生长激素释放激素（GHRH）除了促进生长激素（GH）的合成和释放外，还通过与 GHRH 受体（GHRH-R）及其主要剪接变体 SV1 结合，刺激人类正常细胞和恶性细胞的增殖。GHRH 和 GHRH-Rs 在各种癌症中均有表达，形成了刺激癌细胞生长的途径；此外，SV1 还具有独立于配体的增殖效应。因此，有人提出以 GHRH-Rs 为药理靶点来治疗癌症。目前已开发出各种类型的合成 GHRH 拮抗剂，除了具有抗炎、抗氧化和免疫调节功能外，还具有很强的体外和体内抗癌活性。GHRH 拮抗剂通过阻断垂体 GH/肝脏胰岛素样生长因子 I（IGF-I）轴或直接抑制 GHRH 与肿瘤 GHRH-Rs 的结合来发挥间接作用。此外，GHRH 拮抗剂还能阻断肿瘤细胞中 SV1 的有丝分裂功能。本综述阐述了 GHRH 拮抗剂在实验性人类癌症中抗肿瘤作用的主要发现及其内在机制。开发毒性低、稳定性高的 GHRH 拮抗剂可为治疗癌症和炎症性疾病提供新型治疗药物。

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来源期刊

Reviews in Endocrine & Metabolic Disorders 医学-内分泌学与代谢

CiteScore

14.70

自引率

1.20%

发文量

审稿时长

>12 weeks

期刊介绍： Reviews in Endocrine and Metabolic Disorders is an international journal dedicated to the field of endocrinology and metabolism. It aims to provide the latest advancements in this rapidly advancing field to students, clinicians, and researchers. Unlike other journals, each quarterly issue of this review journal focuses on a specific topic and features ten to twelve articles written by world leaders in the field. These articles provide brief overviews of the latest developments, offering insights into both the basic aspects of the disease and its clinical implications. This format allows individuals in all areas of the field, including students, academic clinicians, and practicing clinicians, to understand the disease process and apply their knowledge to their specific areas of interest. The journal also includes selected readings and other essential references to encourage further in-depth exploration of specific topics.