GHRH and the prostate.

IF 6.9 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Laura Muñoz-Moreno, Irene D Román, Ana M Bajo
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引用次数: 0

Abstract

In the late 1960s and early 1970s, hypothalamic regulatory hormones were isolated, characterized and sequenced. Later, it was demonstrated hypothalamic and ectopic production of growth hormone-releasing hormone (GHRH) in normal and tumor tissues, of both humans and animals. Pituitary-type GHRH receptors (pGHRH-R) had been demonstrated to be expressed predominantly in the anterior pituitary gland but also found in other somatic cells, and significantly present in various human cancers; in addition, the expression of splice variants (SVs) of GHRH receptor (GHRH-R) has been found not only in the pituitary but in extrapituitary tissues, including human neoplasms. In relation to the prostate, besides the pGHRH-R, it has been detected the presence of truncated splice variants of GHRH-R (SV1-SV4) in normal human prostate and human prostate cancer (PCa) specimens; lastly, a novel SV of GHRH-R has been detected in human PCa. Signaling pathways activated by GHRH include AC/cAMP/PKA, Ras/Raf/ERK, PI3K/Akt/mTOR and JAK2/STAT3, which are involved in processes such as cell survival, proliferation and cytokine secretion. The neuropeptide GHRH can also transactivate the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor (HER)-2. Thus, GHRH-Rs have become drug targets for several types of clinical conditions, including prostate-related conditions such as prostatitis, benign hyperplasia and cancer. Over the last fifty years, the development of GHRH-R receptor antagonists has been unstoppable, improving their potency, stability and affinity for the receptor. The last series of GHRH-R antagonists, AVR, exhibits superior anticancer and anti-inflammatory activities in both in vivo and in vitro assays.

GHRH 和前列腺
20 世纪 60 年代末和 70 年代初,人们对下丘脑调节激素进行了分离、鉴定和测序。后来,在人类和动物的正常组织和肿瘤组织中,生长激素释放激素(GHRH)被证实在下丘脑和异位产生。垂体型生长激素受体(pGHRH-R)已被证实主要在垂体前叶表达,但也存在于其他体细胞中,并在各种人类癌症中显著存在;此外,生长激素受体(GHRH-R)的剪接变体(SVs)的表达不仅存在于垂体,也存在于垂体外组织,包括人类肿瘤中。就前列腺而言,除了 pGHRH-R,在正常人前列腺和人前列腺癌(PCa)标本中还发现了 GHRH-R 的截短剪接变体(SV1-SV4);最后,在人 PCa 中发现了一种新型 GHRH-R SV。GHRH激活的信号通路包括AC/cAMP/PKA、Ras/Raf/ERK、PI3K/Akt/mTOR和JAK2/STAT3,它们参与细胞存活、增殖和细胞因子分泌等过程。神经肽 GHRH 还能反式激活表皮生长因子受体(EGFR)和人类表皮生长因子受体(HER)-2。因此,GHRH-Rs 已成为治疗多种临床疾病的药物靶点,包括前列腺炎、良性增生和癌症等前列腺相关疾病。在过去的 50 年中,GHRH-R 受体拮抗剂的开发势不可挡,其药效、稳定性和对受体的亲和力都在不断提高。最后一系列 GHRH-R 拮抗剂 AVR 在体内和体外试验中均表现出卓越的抗癌和抗炎活性。
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来源期刊
Reviews in Endocrine & Metabolic Disorders
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
75
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.
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