GHRH and its analogues in central nervous system diseases.

in Reviews in endocrine & metabolic disorders by Yueyang Liu, Rong Fu, Hui Jia, Kefan Yang, Fu Ren, Ming-Sheng Zhou

TLDR

  • The study reviews the involvement of GHRH in CNS diseases, and explores the potential therapeutic applications of GHRH agonists and antagonists.
  • GHRH agonists may help treat diseases such as Alzheimer's and glioma, while GHRH antagonists may help inhibit tumor growth.

Abstract

Growth hormone-releasing hormone (GHRH) is primarily produced by the hypothalamus and stimulates the release of growth hormone (GH) in the anterior pituitary gland, which subsequently regulates the production of hepatic insulin-like growth factor-1 (IGF-1). GH and IGF-1 have potent effects on promoting cell proliferation, inhibiting cell apoptosis, as well as regulating cell metabolism. In central nerve system (CNS), GHRH/GH/IGF-1 promote brain development and growth, stimulate neuronal proliferation, and regulate neurotransmitter release, thereby participating in the regulation of various CNS physiological activities. In addition to hypothalamus-pituitary gland, GHRH and GHRH receptor (GHRH-R) are also expressed in other brain cells or tissues, such as endogenous neural stem cells (NSCs) and tumor cells. Alternations in GHRH/GH/IGF-1 axis are associated with various CNS diseases, for example, Alzheimer's disease, amyotrophic lateral sclerosis and emotional disorders manifest GHRH, GH or IGF-1 deficiency, and GH or IGF-1 supplementation exerts beneficial therapeutic effects on these diseases. CNS tumors, such as glioma, can express GHRH and GHRH-R, and activating this signaling pathway promotes tumor cell growth. The synthesized GHRH antagonists have shown to inhibit glioma cell growth and may hold promising as an adjuvant therapy for treating glioma. In addition, we have shown that GHRH agonist MR-409 can improve neurological sequelae after ischemic stroke by activating extrapituitary GHRH-R signaling and promoting endogenous NSCs-derived neuronal regeneration. This article reviews the involvement of GHRH/GH/IGF-1 in CNS diseases, and potential roles of GHRH agonists and antagonists in treating CNS diseases.

Overview

  • The main focus of the study is to review the involvement of growth hormone-releasing hormone (GHRH) in central nervous system (CNS) diseases, and explore the potential therapeutic applications of GHRH agonists and antagonists in treating these diseases.
  • The study aims to summarize the current understanding of GHRH's functions in the CNS, including its role in promoting brain development and growth, stimulating neuronal proliferation, and regulating neurotransmitter release.
  • The study also highlights the potential therapeutic applications of GHRH agonists and antagonists in treating various CNS diseases, including Alzheimer's disease, amyotrophic lateral sclerosis, and glioma.

Comparative Analysis & Findings

  • The study reviews the current understanding of GHRH's involvement in various CNS diseases, including Alzheimer's disease, amyotrophic lateral sclerosis, emotional disorders, and glioma.
  • The study found that alterations in the GHRH/GH/IGF-1 axis are associated with these diseases, and that GHRH agonists and antagonists may have therapeutic potential in treating these conditions.
  • The study highlights the results of studies that have shown the beneficial effects of GH or IGF-1 supplementation in these diseases, as well as the inhibitory effects of GHRH antagonists on glioma cell growth.

Implications and Future Directions

  • The study's findings have significant implications for the development of new therapeutic approaches for treating CNS diseases, particularly for those that involve GHRH/GH/IGF-1 dysregulation.
  • Future studies should aim to investigate the mechanisms by which GHRH agonists and antagonists exert their therapeutic effects, in order to optimize their use in clinical practice.
  • Clinical trials are needed to confirm the efficacy and safety of GHRH agonists and antagonists in treating CNS diseases, and to explore their potential as adjuvant therapies.
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