Growth hormone secretagogues: history, mechanism of action, and clinical development

Abstract

Growth hormone secretagogues (GHSs) are a generic term to describe compounds that increase growth hormone (GH) release. GHSs include agonists of the growth hormone secretagogue receptor (GHS‐R), whose natural ligand is ghrelin, and agonists of the growth hormone‐releasing hormone (GHRH) receptor, to which the GHRH binds as a native ligand. Several GHSs have been developed with a view to treating or diagnosing of GH deficiency, which causes growth retardation, gastrointestinal dysfunction, and altered body composition, in parallel with extensive research to identify GHRH, GHS‐R, and ghrelin. This review will focus on the research history and the pharmacology of each GHS, which reached randomized clinical trials. Furthermore, we will highlight the publicly disclosed clinical trials regarding GHSs.

Muscle wasting as an independent predictor of survival in patients with chronic heart failure

“…high-calorie nutritional supplements and branched-chain amino acids), [31][32][33] and possibly anabolic substances. 4,34,35 Unfortunately, none of these interventions have been tested in prospective randomized controlled trials of adequate size so far, but smaller trials suggest that exercise training improves quality of life and the distance covered during the 6 min walk test. 12 Taken together, muscle wasting beyond the cut-offs defined to identify sarcopenia identifies a large proportion of patients with HF who have low muscle strength, quality of life, and exercise capacity and who are likely to become frail in that they may be at increased risk of falling, risk of fractures, and hospitalizations.…”

“…Additional treatment approaches include exercise training (endurance exercise, muscle strength training, and inspiratory muscle training), nutritional support (e.g. high‐calorie nutritional supplements and branched‐chain amino acids), 31–33 and possibly anabolic substances 4,34,35 . Unfortunately, none of these interventions have been tested in prospective randomized controlled trials of adequate size so far, but smaller trials suggest that exercise training improves quality of life and the distance covered during the 6 min walk test 12 …”

G protein-coupled receptors: structure- and function-based drug discovery

“… 44 , 45 Tesamorelin, another synthetic form of GHRH, was approved in 2010 to treat human immunodeficiency virus (HIV)-associated lipodystrophy. 44 …”

“…42,43 Two approved diagnostic agents are analogs of CRF (corticorelin ovine triflutate peptide) and GHRH (sermorelin) for diagnosis of Cushing's disease or ectopic adrenocorticotropic hormone syndrome and growth hormone deficiency, respectively. 44,45 Tesamorelin, another synthetic form of GHRH, was approved in 2010 to treat human immunodeficiency virus (HIV)associated lipodystrophy. 44 PTH analogs, teriparatide and abaloparatide, were approved in 2002 and 2017, respectively, for postmenopausal osteoporosis with similar side effects.…”

“…44,45 Tesamorelin, another synthetic form of GHRH, was approved in 2010 to treat human immunodeficiency virus (HIV)associated lipodystrophy. 44 PTH analogs, teriparatide and abaloparatide, were approved in 2002 and 2017, respectively, for postmenopausal osteoporosis with similar side effects. However, abaloparatide binds to parathyroid hormone 1 receptor (PTH1R) with higher affinity and selectivity that resulted in greater bone density.…”