Signaling mechanism of growth hormone-releasing hormone receptor.

Gabor Halmos, Zsuzsanna Szabo, Eva Juhasz, Andrew V Schally

Journal: Vitamins and hormones 2023;123():1-26

PMID: 37717982

Full Text on Elsevier Science View on PubMed

Abstract

The hypothalamic peptide 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. Splice variants of GHRH-Rs (SV) in human tumors and other extra pituitary tissues were identified 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 GHRH stimulation. A large body of work have evaluated potential clinical applications of agonists and antagonists of GHRH in diverse fields, including endocrinology, oncology, cardiology, diabetes, obesity, metabolic dysfunctions, Alzheimer's disease, ophthalmology, wound healing and other applications. In this chapter, we briefly review the expression and potential function of GHRH-Rs and their SVs in various tissues and also elucidate and summarize the activation, molecular mechanism and signalization pathways of these receptors. Therapeutic applications of GHRH analogs are also discussed.

Address: Department of Biopharmacy, Faculty of Pharmacy, University of Debrecen, Debrecen, Hungary; Veterans Affairs Medical Center, Endocrine, Polypeptide and Cancer Institute, Miami, FL, United States. Electronic address: [email protected].; Department of Biopharmacy, Faculty of Pharmacy, University of Debrecen, Debrecen, Hungary.; Department of Pediatrics, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.; Veterans Affairs Medical Center, Endocrine, Polypeptide and Cancer Institute, Miami, FL, United States; Department of Pathology, Miller School of Medicine, University of Miami, Miami, FL, United States; Department of Medicine, Divisions of Hematology-Oncology and Endocrinology, Miller School of Medicine, University of Miami, Miami, FL, United States; Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, United States.

DOI: 10.1016/bs.vh.2023.06.004

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MeSH Terms: Humans, Growth Hormone, Receptors, Neuropeptide, Receptors, Pituitary Hormone-Regulating Hormone, Signal Transduction