Reviews in Endocrine & Metabolic Disorders最新文献

GHRH is a neuropeptide associated with a diverse variety of activities in human physiology and immune responses. The present study reviews the latest information on the involvement of GHRH in the immune system and inflammation, suggesting that GHRH antagonists may deliver a new therapeutic possibility in disorders related to immune system dysfunction and inflammation.

Despite over a century of insulin therapy and recent advances in glucose monitoring, diabetes and its complications remain a significant burden. Current medications are not durable, with symptoms often returning after treatment ends, and responses vary between patients. Additionally, the effectiveness of many medications diminishes over time, highlighting the need for alternative approaches. Maintaining β-cell mass and promoting β-cell regeneration offer more curable treatments, while cell replacement therapies could be an option if regeneration is not feasible. For both strategies, enhancing β-cell survival is crucial. Growth hormone-releasing hormone (GHRH) was originally discovered for its ability to stimulate the production and release of growth hormone (GH) from the pituitary. Beyond the hypothalamus, GHRH is produced in peripheral tissues, with its receptor, GHRHR, expressed in tissues such as the pituitary, pancreas, adipose tissue, intestine, and liver. Several studies have shown that GHRH and its analogs enhance the survival of insulin-producing pancreatic β-cells both in vitro and in animal models. These beneficial effects strongly support the potential of GHRH agonists and antagonists for the clinical treatment of human metabolic diseases or for enhancing β-cell survival in cells used for transplantation. In the current review, we will discuss the roles of hypothalamic and extrahypothalamic GHRH in metabolism in physiological and pathological contexts, along with the underlying mechanisms. Furthermore, we will discuss the potential beneficial effects of GHRH analogs for the treatment of metabolic diseases.

Growth hormone-releasing hormone (GHRH) has classically been considered a regulatory neuropeptide of the hypothalamic-pituitary system, which mediates its anabolic effects through hepatic GH/IGF-I axis. However, during the last decades it has been demonstrated that this key regulatory hormone may be produced in numerous peripheral tissues outside the central nervous system, participating in fundamental physiological functions through a complex balance between its purely endocrine action, and the recently local (autocrine/paracrine) discovered role. Among peripheral sites, its presence in the male and female reproductive systems stands out. In this review, we will first explore the role of the GHRH/GHRH-R hormone axis as a central player in the gonadal function; then, we will discuss available information regarding the presence of GHRH/GHRH-R and the potential physiological roles in reproductive systems of various species; and finally, we will address how reproductive system-related disorders-such as infertility problems, endometriosis, or tumor pathologies (including prostate, or ovarian cancer)-could benefit from hormonal interventions related to the manipulation of the GHRH axis.

Growth hormone (GH)-releasing hormone (GHRH), a hypothalamic peptide initially characterized for its role in GH regulation, has gained increasing attention due to its GH-independent action on peripheral physiology, including that of the cardiovascular system. While its effects on the peripheral vasculature are still under investigation, GHRH and synthetic agonists have exhibited remarkable receptor-mediated cardioprotective properties in preclinical models. GHRH and its analogs enhance myocardial function by improving contractility, reducing oxidative stress, inflammation, and offsetting pathological remodeling. Studies performed in small and large animal models have demonstrated the efficacy of these compounds in diverse cardiomyopathies, suggesting their potential as promising therapeutic agents. However, the clinical translation of GHRH synthetic analogs still faces challenges related to the route of administration and potential side effects mainly associated with activation of the GH/IGF-I axis. Despite these hurdles, the compelling evidence supporting their role in cardiac repair makes GHRH analogs attractive candidates for clinical testing in the treatment of various cardiac diseases.

This review focuses on our current understanding of how growth hormone releasing hormone (GHRH): 1) stimulates GH release and synthesis from pituitary growth hormone (GH)-producing cells (somatotropes), 2) drives somatotrope proliferation, 3) is negatively regulated by somatostatin (SST), GH and IGF1, 4) is altered throughout lifespan and in response to metabolic challenges, and 5) analogues can be used clinically to treat conditions of GH excess or deficiency. Although a large body of early work provides an underpinning for our current understanding of GHRH, this review specifically highlights more recent work that was made possible by state-of-the-art analytical tools, receptor-specific agonists and antagonists, high-resolution in vivo and ex vivo imaging and the development of tissue (cell) -specific ablation mouse models, to paint a more detailed picture of the regulation and actions of GHRH.

Growth Hormone-Releasing Hormone (GHRH) and its analogs have gained significant attention for their therapeutic potential across various domains, including oncology, regenerative medicine, and metabolic disorders. Originally recognized for its role in regulating growth hormone (GH) secretion, GHRH has since been discovered to exert broader physiological effects beyond the pituitary gland, with GHRH receptors identified in multiple extrahypothalamic tissues, including tumor cells. This review explores the development of both GHRH agonists and antagonists, focusing on their mechanisms of action, therapeutic applications, and future potential. GHRH agonists have shown promise in promoting tissue regeneration, improving cardiac function, and enhancing islet survival in diabetes. Meanwhile, GHRH antagonists, particularly those in the MIA and AVR series, demonstrate potent antitumor activity by inhibiting cancer cell proliferation and downregulating growth factor pathways, while also exhibiting anti-inflammatory properties. Preclinical studies in models of lung, prostate, breast, and gastrointestinal cancers indicate that GHRH analogs could offer a novel therapeutic approach with minimal toxicity. Additionally, GHRH antagonists are being investigated for their potential in treating neurodegenerative diseases and inflammatory conditions. This review highlights the versatility of GHRH analogs as a promising class of therapeutic agents, poised to impact multiple fields of medicine.

Despite initial discovery in pancreatic tumors, GHRH is a 44-amino acid peptide primarily expressed in the hypothalamus. Recent RNA sequencing clarifies GHRH expression: predominantly hypothalamic in humans, with some basal ganglia presence, while extending to additional central nervous system (CNS) regions in other species. GHRH binds to its G-protein coupled receptor (GHRHR) in the arcuate (ARC), ventromedial (VMH), and periventricular (PeN) nuclei of the hypothalamus to exert its effects. Notably, the highest non-brain expression is found in somatotroph cells of the pituitary, directly targeting growth hormone (GH) production. GHRH is the primary regulator of pulsatile GH secretion, counteracted by somatostatin. While early models proposed alternating GHRH/somatostatin bursts, others implicate somatostatin as the primary regulator of GH pulse timing. These models fail to fully explain species and gender differences, particularly regarding nutritional status. The discovery of ghrelin, acting via GHS-R1a on GHRH neurons, significantly advanced understanding of GH regulation. Ghrelin interacts intricately with GHRH, modulating its expression and neuronal activity. Ghrelin also exerts GHRH-independent GH stimulation and synergizes with GHRH. The crucial role of GHRH in GH regulation is demonstrated by its key involvement in the action of other GH regulators, such as leptin, neuropeptide Y (NPY), and orexins. However, these interactions have also revealed that the physiological effects of GHRH extend far beyond its canonical role as a GH secretagogue. In this context, GHRH is thought to be a key regulator of the sleep-wake cycle and may be involved in whole-body energy homeostasis. The objective of this review is to summarize the current knowledge on GHRH and to discuss the potential pleiotropic effect of this hypothalamic neuropeptide, far beyond its classical action as regulator of the somatotroph axis.

Growth hormone-releasing hormone (GHRH) is a crucial endocrine hormone that exerts its biological effects by binding to specific receptors on the cell surface, known as GHRH receptors (GHRH-R). This binding activates downstream signaling pathways. In addition to promoting growth hormone secretion by the pituitary gland, GHRH also functions to maintain multisystem homeostasis by interacting with peripheral tissues that express GHRH-R. Due to the multiple roles of GHRH in body development and tissue repair, a variety of GHRH analogue peptides have been synthesized. Based on their effects on GHRH-R, these GHRH analogues can be classified as GHRH-R agonists and antagonists. Recently, the interaction of GHRH and its analogues with blood vessels, such as promoting angiogenesis and inhibiting vascular calcification (VC), has gained significant attention. This article reviews the effects of GHRH and its analogues on blood vessels.

The hypothalamic polypeptide 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. Various splice variants of GHRH-R (SV) in human neoplasms and other extrapituitary tissues were demonstrated 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 stimulation by GHRH. In this review, we briefly discuss the activation, regulation, molecular mechanisms and signaling pathways of GHRH-Rs and their SVs in various tissues and also summarize the expression, biological activities and potential function of GHRH, its analogs and their receptors. A large body of work have extensively studied and evaluated potential clinical applications of agonists and antagonists of GHRH in diverse fields, including oncology, endocrinology, obesity, diabetes, other metabolic dysfunctions, cardiology, immune functions, mood disorders, Alzheimer's and lung disease, ophthalmology, inflammation, wound healing and other applications. These results strongly support the potential therapeutic use of GHRH analogs in human medicine in the near future.