Growth Hormone Secretagogues as Potential Therapeutic Agents to Restore Growth Hormone Secretion in Older Subjects to Those Observed in Young Adults

The discovery of the growth hormone secretagogues (GHS) and the reverse pharmacology leading to the discovery of GHS receptor which enabled the identification of ghrelin as the natural ligand for the receptor have opened a new horizon in growth hormone (GH) physiology, pathophysiology, and therapeut...

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Bibliographic Details
Published in:The journals of gerontology. Series A, Biological sciences and medical sciences Biological sciences and medical sciences, 2023-06, Vol.78 (Suppl 1), p.38-43
Main Authors: Smith, Roy G, Thorner, Michael O
Format: Article
Language:English
Subjects:
Aged
Fat-free body mass
Fatty liver
Ghrelin
Growth Hormone
Growth Hormone-Releasing Hormone - pharmacology
Growth Hormone-Releasing Hormone - physiology
Growth hormones
Human Growth Hormone - metabolism
Human Growth Hormone - therapeutic use
Humans
Ligands
Liver diseases
Osteoporosis
Pathophysiology
Pharmacology
Secretagogues
Supplement : Function-Promoting Therapies
Young Adult
Young adults
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Summary:The discovery of the growth hormone secretagogues (GHS) and the reverse pharmacology leading to the discovery of GHS receptor which enabled the identification of ghrelin as the natural ligand for the receptor have opened a new horizon in growth hormone (GH) physiology, pathophysiology, and therapeutics. Major progress has been made and we now have orally active GHS which are able to restore optimal pulsatile GH secretion which cannot be overstimulated as insulin-like growth factor feedback regulates the peaks to the optimum level. This enables GH to be restored in the older to levels normally seen in 20- to 30-year-old people; this leads to an increase in fat-free mass and redistribution of fat to the limbs. As these agents are ultimately approved and investigated further, it is likely that they will be shown to restore growth in children with moderate-to-mild GH deficiency; their benefits will be investigated in other indications such as nonalcoholic fatty liver disease, frailty, anemia, osteoporosis, and immune compromise in older subjects. The exquisite regulation of GH secretion reflects the importance of GH pulsatility in the regulation of somatotroph action of GH.
ISSN:1079-5006
1758-535X
DOI:10.1093/gerona/glad022