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Journal Article Review Ppublish 2 citations

PubMed: 39934495 DOI: 10.1007/s11154-025-09952-x

Growth hormone-releasing hormone receptor (GHRH-R) and its signaling.

Rev Endocr Metab Disord 26(3):343-352

Authors: Gabor Halmos, Zsuzsanna Szabo, Nikoletta Dobos, Eva Juhasz, Andrew V Schally

Affiliations

  • Department of Biopharmacy, Faculty of Pharmacy, University of Debrecen, Rex u. 10, Debrecen, 4032, Hungary.
  • Veterans Affairs Medical Center, Endocrine, Polypeptide and Cancer Institute, Miami, FL, 33125, USA.
  • Department of Biopharmacy, Faculty of Pharmacy, University of Debrecen, Rex u. 10, Debrecen, 4032, Hungary.
  • Department of Pediatrics, Faculty of Medicine, University of Debrecen, Debrecen, 4032, Hungary.
  • Veterans Affairs Medical Center, Endocrine, Polypeptide and Cancer Institute, Miami, FL, 33125, USA. Department of Pathology, Department of Medicine, Divisions of Hematology-Oncology and Endocrinology, Miller School of Medicine, University of Miami, Miami, FL, 33101, USA. Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, 33136, USA.

Abstract

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.

MeSH

Growth Hormone-Releasing Hormone, Growth, Hormones, Tissues, Growth Hormone, Endocrine System Diseases

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