Actions and Potential Therapeutic Applications of Growth Hormone-Releasing Hormone Agonists

Andrew V. Schally, Xianyang Zhang, Renzhi Cai, Joshua Hare, Riccarda Granata, Manuela Bartoli

Research output: Contribution to journalArticle

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Abstract

In this article, we briefly review the identification of GHRH, provide an abridged overview of GHRH antagonists, and focus on studies with GHRH agonists. Potent GHRH agonists of JI and MR class were synthesized and evaluated biologically. Besides the induction of the release of pituitary GH, GHRH analogs promote cell proliferation and exert stimulatory effects on various tissues, which express GHRH receptors (GHRH-Rs). A large body of work shows that GHRH agonists, such as MR-409, improve pancreatic β-cell proliferation and metabolic functions and facilitate engraftment of islets after transplantation in rodents. Accordingly, GHRH agonists offer a new therapeutic approach to treating diabetes. Various studies demonstrate that GHRH agonists promote repair of cardiac tissue, producing improvement of ejection fraction and reduction of infarct size in rats, reduction of infarct scar in swine, and attenuation of cardiac hypertrophy in mice, suggesting clinical applications. The presence of GHRH-Rs in ocular tissues and neuroprotective effects of GHRH analogs in experimental diabetic retinopathy indicates their possible therapeutic applications for eye diseases. Other effects of GHRH agonists, include acceleration of wound healing, activation of immune cells, and action on the central nervous system. As GHRH might function as a growth factor, we examined effects of GHRH agonists on tumors. In vitro, GHRH agonists stimulate growth of human cancer cells and upregulate GHRH-Rs. However, in vivo, GHRH agonists inhibit growth of human cancers xenografted into nude mice and downregulate pituitary and tumoral GHRH-Rs. Therapeutic applications of GHRH analogs are discussed. The development of GHRH analogs should lead to their clinical use.

Original languageEnglish (US)
Pages (from-to)1600-1612
Number of pages13
JournalEndocrinology
Volume160
Issue number7
DOIs
StatePublished - Jul 1 2019

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Growth Hormone-Releasing Hormone
Action Potentials
Cell Proliferation
Islets of Langerhans Transplantation
Neoplasms
Eye Diseases
Cardiomegaly
Neuroprotective Agents
Diabetic Retinopathy
Growth
Nude Mice
Wound Healing
Cicatrix
Rodentia
Intercellular Signaling Peptides and Proteins
Up-Regulation
Swine
Therapeutics
Down-Regulation
Central Nervous System

ASJC Scopus subject areas

  • Endocrinology

Cite this

Actions and Potential Therapeutic Applications of Growth Hormone-Releasing Hormone Agonists. / Schally, Andrew V.; Zhang, Xianyang; Cai, Renzhi; Hare, Joshua; Granata, Riccarda; Bartoli, Manuela.

In: Endocrinology, Vol. 160, No. 7, 01.07.2019, p. 1600-1612.

Research output: Contribution to journalArticle

Schally, Andrew V. ; Zhang, Xianyang ; Cai, Renzhi ; Hare, Joshua ; Granata, Riccarda ; Bartoli, Manuela. / Actions and Potential Therapeutic Applications of Growth Hormone-Releasing Hormone Agonists. In: Endocrinology. 2019 ; Vol. 160, No. 7. pp. 1600-1612.
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