— Research note —
GHRP-2
Synthetic hexapeptide ghrelin receptor agonist investigated for potent growth hormone-releasing activity with characterized cortisol and prolactin effects.
GHRP-2 (growth hormone-releasing peptide-2), also designated pralmorelin, is a synthetic hexapeptide (D-Ala-D-2-Nal-Ala-Trp-D-Phe-Lys-NH2) developed in the 1980s by Cyril Bowers and colleagues at Tulane University. The molecule was among the second-generation GHRPs designed to retain the growth hormone-releasing potency of GHRP-6 while improving stability and oral bioavailability characteristics. GHRP-2 advanced through clinical research in the 1990s and 2000s and remains approved as a diagnostic agent for growth hormone deficiency in Japan.
In pharmacological characterization, GHRP-2 produces robust growth hormone pulses upon subcutaneous, intravenous, intranasal, or oral administration in research models. Compared with the more selective ipamorelin, GHRP-2 shows greater stimulation of cortisol and prolactin release at doses producing comparable growth hormone responses, a profile reflecting broader engagement of central and peripheral pathways downstream of ghrelin receptor activation. This pharmacological signature distinguishes GHRP-2 in head-to-head studies and shapes its utility as a research tool.
The compound has been used extensively in clinical research as a diagnostic probe for pituitary function, with the Japanese GHRP-2 test (using a 100-microgram dose for growth hormone reserve assessment) being a notable application. Academic research has employed GHRP-2 in combination pharmacology studies with GHRH analogs, where the two-receptor synergy produces growth hormone responses substantially greater than either agent alone, and in mechanistic studies of central appetite and energy balance regulation.
GHRP-2 is supplied here for laboratory research use only and is not intended for human consumption. Its primary research applications include pituitary pharmacology, comparative GHRP characterization, and diagnostic test modeling.
Mechanism
GHRP-2 binds the growth hormone secretagogue receptor type 1a (GHSR-1a) on pituitary somatotrophs, activating Gq-mediated phospholipase C signaling, elevating intracellular calcium, and triggering exocytosis of stored growth hormone. The hexapeptide also engages central nervous system GHSR-1a, contributing to the appetite-stimulating effects observed in preclinical models and to modest activation of the hypothalamic-pituitary-adrenal axis.
Mechanistic comparisons with ipamorelin have attributed the greater cortisol and prolactin response of GHRP-2 to broader engagement of central neuropeptide systems and possibly to activity at additional receptors beyond GHSR-1a. The downstream cortisol elevation appears to result from activation of corticotropin-releasing hormone neurons in the paraventricular nucleus rather than direct adrenocortical stimulation. Prolactin release likely reflects engagement of lactotrophs through indirect hypothalamic mechanisms.
Research history
Cyril Bowers and colleagues at Tulane University developed the GHRP family in the 1980s through systematic structure-activity exploration of met-enkephalin analogs with growth hormone-releasing activity. GHRP-2 was disclosed in the late 1980s and early 1990s as an optimized hexapeptide with improved potency and stability relative to the parent GHRP-6.
Clinical research advanced through the 1990s with phase 1 and phase 2 studies in pediatric growth disorders and adult growth hormone deficiency. GHRP-2 received approval in Japan in 2007 as the diagnostic agent pralmorelin (under the brand name GHRP Kaken) for growth hormone reserve testing. Outside Japan, the molecule did not advance to broader regulatory approval despite extensive characterization.
The discovery of the endogenous ghrelin ligand by Kojima and colleagues in 1999 contextualized the GHRP class as synthetic agonists of a previously orphan receptor, transforming the research framework. Subsequent academic studies have used GHRP-2 in combination pharmacology with GHRH analogs, in appetite and energy balance research, and as a reference compound in ghrelin receptor pharmacology. The molecule continues to appear in research-chemical catalogs and in peer-reviewed pituitary pharmacology studies.
References
- Bowers CY, et al. 1990. On the in vitro and in vivo activity of a new synthetic hexapeptide that acts on the pituitary to specifically release growth hormone. Endocrinology. PMID: 2335078
- Kojima M, et al. 1999. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. PMID: 10604470
- Furuta S, et al. 2004. Pharmacokinetics and metabolism of [14C]KP-102 (GHRP-2) in rats. Xenobiotica. PMID: 15527937
- Chihara K, et al. 2007. Efficacy and safety of growth hormone-releasing peptide-2 (GHRP-2) test for diagnosis of growth hormone deficiency in adults. Endocr J. PMID: 17878591
- Smith RG. 2005. Development of growth hormone secretagogues. Endocr Rev. PMID: 15814848
- Sinha DK, et al. 2008. Beyond the androgen receptor: the role of growth hormone secretagogues. Curr Drug Targets.
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Information presented in third-person scientific context. Research use only. Not medical advice; not for human consumption.