GHRP-2: research background
What GHRP-2 is
Pralmorelin, also known as GHRP-2, is a synthetic growth hormone-releasing peptide developed by Polygen and Tulane University. It is an orally active compound (PMID 15230633). GHRP-2 is a hexapeptide (D-Ala-D-(beta-naphthyl)-Ala-Ala-Trp-D-Phe-Lys-NH(2)) (PMID 20552695). GHRP-2 is one of several growth hormone-releasing peptides (GHRPs), which are synthetic, non-natural peptides that stimulate somatotrope secretion (PMID 9186261). It mimics the actions of ghrelin, a natural peptide that regulates growth hormone (GH) release (PMID 15230633).
How it is thought to work
GHRP-2, like other GHRPs, stimulates GH release via a specific GHRP-like receptor, which has been cloned (PMID 9849822, PMID 9186261). This receptor is present at both the pituitary and hypothalamic levels in animals and humans (PMID 9186261). GHRPs may act by counteracting somatostatinergic activity in the pituitary and hypothalamus, and/or partly through a GHRH-mediated mechanism (PMID 9186261). The GHRP receptor does not share sequence homology with other known G-protein-coupled receptors (PMID 9186261).
Laboratory and animal studies
In vitro, GHRP-2 was found to have higher potency but lower efficacy compared to ipamorelin or GHRP-6 in releasing GH from primary rat pituitary cells (PMID 9849822). In conscious swine, GHRP-2 released GH with an ED50 of 0.6 nmol/kg and an Emax of 56+/-6 ng GH/ml plasma (animal study, PMID 9849822). Unlike ipamorelin, administration of GHRP-2 in swine resulted in increased plasma levels of ACTH and cortisol (animal study, PMID 9849822). A physiologically based pharmacokinetic model for pralmorelin hydrochloride in rats showed rapid plasma decline and rapid biliary excretion, with 80% of the dose recovered unchanged in bile within one hour (animal study, PMID 16033952). The distribution of pralmorelin into the liver in rats was blood flow-limited, while in other tissues it was permeability-limited (animal study, PMID 16033952). Researchers have studied the structure-activity relationship for peptidic GHRPs, including GHRP-2, concerning their interaction with the GHSR1a receptor (PMID 26811125).
Human evidence and applications
Pralmorelin can markedly increase plasma GH levels in healthy human subjects, regardless of gender, obesity, or age (human study, PMID 15230633). In patients with GH deficiency, the effect of pralmorelin on GH levels is significantly lower compared to healthy controls (human study, PMID 15230633). A cut-off threshold of 15.0 micro g/L for the GH peak has been identified for diagnosing GH deficiency (human study, PMID 15230633). GHRP-2 is used intravenously as a diagnostic agent for GH deficiency (human application, PMID 20552695). Following intravenous administration in ten male volunteers, unchanged GHRP-2 and its specific metabolite, AA-3, were detected in urine (human study, PMID 20552695). GHRP-2 has been detected in human urine for up to 47 hours after nasal administration, along with its metabolites GHRP-2 free acid and GHRP-2 (1-3) free acid (human study, PMID 25869809).
Open questions and limitations
GHRP-2, along with other GHRPs, is listed on the World Anti-Doping Agency (WADA) Prohibited List due to its potential for misuse by athletes in expectation of a growth-promoting effect (PMID 20552695, PMID 25869809). The mechanisms underlying the GHRP effect are still unclear, with the possibility of an unknown hypothalamic factor being involved (PMID 9186261). While GHRP-2 can stimulate GH and IGF-1, current data on its clinical efficacy as an adjunctive therapy for conditions like male hypogonadism largely remain lacking, limiting understanding of its role in treatment (PMID 32257855).
Key terms explained
Somatotrope secretion: The release of growth hormone from the pituitary gland. GHRP-like receptor: A specific receptor in the body that binds to growth hormone-releasing peptides and triggers growth hormone release. Hypothalamic level: Refers to the hypothalamus, a part of the brain that regulates various bodily functions, including hormone release. Pituitary level: Refers to the pituitary gland, a small gland at the base of the brain that produces and releases hormones. Somatostatinergic activity: The activity related to somatostatin, a hormone that inhibits the release of growth hormone.
Studies cited in this section
- Pralmorelin: GHRP 2, GPA 748, growth hormone-releasing peptide 2, KP-102 D, KP-102 LN, KP-102D, KP-102LN. — Drugs in R&D, 2004 (PMID 15230633)
- Ipamorelin, the first selective growth hormone secretagogue. — European journal of endocrinology, 1998 (PMID 9849822)
- Determination of growth hormone secretagogue pralmorelin (GHRP-2) and its metabolite in human urine by liquid chromatography/electrospray ionization tandem mass spectrometry. — Rapid communications in mass spectrometry : RCM, 2010 (PMID 20552695)
- Growth hormone-releasing peptides. — European journal of endocrinology, 1997 (PMID 9186261)
- Structure-activity relationship for peptídic growth hormone secretagogues. — Drug testing and analysis, 2017 (PMID 26811125)
- Determination of growth hormone releasing peptides metabolites in human urine after nasal administration of GHRP-1, GHRP-2, GHRP-6, Hexarelin, and Ipamorelin. — Drug testing and analysis, 2015 (PMID 25869809)
- Beyond the androgen receptor: the role of growth hormone secretagogues in the modern management of body composition in hypogonadal males. — Translational andrology and urology, 2020 (PMID 32257855)
- Physiologically based pharmacokinetic model for pralmorelin hydrochloride in rats. — Drug metabolism and disposition: the biological fate of chemicals, 2005 (PMID 16033952)
Summarised from the PubMed abstracts listed above. Educational reference only — not medical advice or instructions.
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