Review
Growth hormone-releasing hormone receptor (GHRH-R) and its signaling
Gabor Halmos et al. Rev Endocr Metab Disord. 2025 Jun.
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.
Keywords: GHRH receptor (GHRH-R); Growth hormone-releasing hormone (GHRH); Signalization; Splice variants (SVs).
© 2025. The Author(s).
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Conflict of interest statement
Declarations. Competing interests: The authors declare no competing interests.
Figures Fig. 1
Amino acid sequences of human GHRH (GHRH 1–44). The full biological activity is retained in the N-terminal 29 amino acid sequence [GHRH(1–29)NH2] Fig. 2
Schematic drawing and summary diagram of the potential role and signaling mechanisms, cascades and cellular effects of GHRH, GHRH agonists and GHRH antagonists mediated by GHRH-R and SV1
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