TITLE:
Growth Hormone Secretagogues: Between Endocrine Physiology and the Therapeutic Frontier of GH-IGF-1 Axis-Modulating Peptides
AUTHORS:
Pedro Augusto Zaiats Junior, Pedro Senteio, Diego Ribeiro, Kerly Martendal
KEYWORDS:
Growth Hormone, Growth Hormone Secretagogues, GHRP, GH-IGF-1 Axis, Therapeutic Peptides
JOURNAL NAME:
Open Journal of Clinical Diagnostics,
Vol.16 No.3,
July
31,
2026
ABSTRACT: Growth hormone (GH) plays a central role in the regulation of somatic growth, body composition, energy metabolism, bone homeostasis, and cardiovascular function. Physiological GH secretion is controlled by a complex interplay of hypothalamic factors, primarily growth hormone-releasing hormone (GHRH) and somatostatin, as well as ghrelin and several metabolic and hormonal modulators. Over the past decades, the development of growth hormone secretagogues (GHSs) has significantly expanded the possibilities for pharmacological modulation of the GH-insulin-like growth factor 1 (GH-IGF-1) axis. Growth hormone secretagogues comprise a heterogeneous class of compounds capable of stimulating endogenous GH secretion through activation of the growth hormone secretagogue receptor (GHS-R1a). This group includes synthetic peptides such as GHRP-2, GHRP-6, hexarelin, and ipamorelin, as well as non-peptide molecules such as ibutamoren (MK-677). More recently, novel peptide analogs and combination therapeutic strategies have been developed to optimize the somatotropic response while minimizing off-target effects on other endocrine pathways. This review summarizes the physiological mechanisms regulating the GH-IGF-1 axis, the pharmacological characteristics of the major growth hormone secretagogues currently available, their established and emerging clinical applications, and the current evidence regarding their efficacy and safety. In addition, it discusses future therapeutic perspectives, as well as the regulatory and ethical challenges associated with the use of these compounds in regenerative medicine, healthy aging, and physical performance enhancement.