The development of growth hormone-releasing hormone analogs: Therapeutic advances in cancer, regenerative medicine, and metabolic disorders DOI Creative Commons
Andrew V. Schally,

Renzhi Cai,

Xianyang Zhang

et al.

Reviews in Endocrine and Metabolic Disorders, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 26, 2024

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

Language: Английский

Growth hormone-releasing hormone receptor (GHRH-R) and its signaling DOI Creative Commons

Gábor Halmos,

Zsuzsanna Szabó, Nikoletta Dobos

et al.

Reviews in Endocrine and Metabolic Disorders, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 12, 2025

Abstract The hypothalamic polypeptide growth hormone-releasing hormone (GHRH) stimulates the secretion of (GH) from pituitary through binding and activation type GHRH receptor (GHRH-R), which belongs to family G protein-coupled receptors with seven potential membrane-spanning domains. Various splice variants GHRH-R (SV) in human neoplasms other extrapituitary tissues were demonstrated their cDNA was sequenced. Among SVs, variant 1 (SV1) possesses greatest similarity full-length remains functional by eliciting cAMP signaling mitogenic activity upon stimulation GHRH. In this review, we briefly discuss activation, regulation, molecular mechanisms pathways GHRH-Rs SVs various also summarize expression, biological activities function GHRH, its analogs receptors. A large body work have extensively studied evaluated clinical applications agonists antagonists diverse fields, including oncology, endocrinology, obesity, diabetes, metabolic dysfunctions, cardiology, immune functions, mood disorders, Alzheimer’s lung disease, ophthalmology, inflammation, wound healing applications. These results strongly support therapeutic use medicine near future.

Language: Английский

Citations

2
Update on regulation of GHRH and its actions on GH secretion in health and disease DOI
Antonio J. Montero‐Hidalgo, Mercedes del Río-Moreno, Jesús M. Pérez‐Gómez

et al.

Reviews in Endocrine and Metabolic Disorders, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 21, 2025

Language: Английский

Citations

1
GHRH in diabetes and metabolism DOI Creative Commons
Charlotte Steenblock, Stefan R. Bornstein

Reviews in Endocrine and Metabolic Disorders, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 19, 2024

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

Language: Английский

Citations

4
Mention to Prof. Andrew V. Schally DOI Creative Commons
Riccarda Granata

Reviews in Endocrine and Metabolic Disorders, Journal Year: 2025, Volume and Issue: unknown

Published: March 17, 2025

Language: Английский

Citations

0
Growth Hormone-Releasing Hormone Antagonists Increase Radiosensitivity in Non-Small Cell Lung Cancer Cells DOI Open Access
Iacopo Gesmundo, Francesca Pedrolli, F.R. Giglioli

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3267 - 3267

Published: April 1, 2025

Growth hormone-releasing hormone (GHRH) antagonists exert antitumor functions in different experimental cancers. However, their role combination with radiotherapy non-small cell lung cancer (NSCLC) remains unknown. Therefore, we investigated the radiosensitizing effect of GHRH NSCLC. A549 and H522 NSCLC lines were exposed to ionizing radiation (IR) MIA-602 MIA-690, either individually or combination. Cell viability proliferation evaluated by MTT, BrdU, flow cytofluorimetry, clonogenic assays; gene protein expression, signaling pathways, apoptosis analyzed real-time PCR, Western blot, annexin staining, caspase-3 assay. showed effects alone potentiated IR-induced inhibition proliferation. The MIA-690 IR decreased expression receptor, its oncogenic splice variant 1, IGF1 mRNA levels. Additionally, cycle inhibitors proapoptotic markers upregulated, whereas cyclins, MYC, antiapoptotic Bcl-2 downregulated. Radioresistance was prevented which also blunted epithelial-mesenchymal transition enhancing E-cadherin reducing mesenchymal, oxidative, proangiogenic effectors. Finally, both enhanced radiosensitivity primary human cells. These findings highlight potential as radiosensitizers treatment.

Language: Английский

Citations

0
Impact of corticoid receptors on Alzheimer’s disease: a neuroendocrine perspective DOI
Falguni Goel,

Daksh Kumar,

Anushka Sharma

et al.

Inflammopharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: April 18, 2025

Language: Английский

Citations

0
The development of growth hormone-releasing hormone analogs: Therapeutic advances in cancer, regenerative medicine, and metabolic disorders DOI Creative Commons
Andrew V. Schally,

Renzhi Cai,

Xianyang Zhang

et al.

Reviews in Endocrine and Metabolic Disorders, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 26, 2024

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

Language: Английский

Citations

3