GHRP-1
GHRP-1 is the first synthetic growth hormone releasing peptide discovered by Cyril Bowers, acting as a ghrelin receptor agonist with historical significance in the discovery of the GHS-R1a receptor and endogenous ghrelin.
GHRP-1 (Growth Hormone Releasing Peptide-1) is a synthetic hexapeptide and the first growth hormone secretagogue discovered by Cyril Bowers in the 1970s-1980s. Its identification as a potent stimulator of growth hormone release from the anterior pituitary directly led to the discovery of the growth hormone secretagogue receptor (GHS-R1a) and ultimately to the identification of ghrelin, the endogenous ligand for that receptor.
Overview
GHRP-1 was among the first synthetic peptides demonstrated to stimulate growth hormone release independent of the GHRH pathway. Bowers and colleagues systematically modified enkephalin-derived peptides, discovering that certain hexapeptide configurations could potently release GH from pituitary somatotrophs through a then-unknown receptor. This work ultimately established an entirely new axis of GH regulation alongside GHRH and somatostatin. GHRP-1 is less commonly used in contemporary research compared to GHRP-2 and GHRP-6, which offer greater potency and better-characterized pharmacology.
Mechanism of Action
GHRP-1 binds to the growth hormone secretagogue receptor type 1a (GHS-R1a), a G protein-coupled receptor expressed primarily on pituitary somatotrophs. Receptor activation triggers intracellular calcium mobilization via the phospholipase C/inositol trisphosphate pathway, leading to GH vesicle exocytosis. GHRP-1 acts through a mechanism distinct from GHRH, which signals through the GHRH receptor via cAMP/protein kinase A. This independent mechanism allows GHRPs to synergize with GHRH for amplified GH release. GHRP-1 also demonstrated cardioprotective activity in fetal heart cell cultures, reducing apoptosis through mechanisms shared with other GHRPs (Muccioli et al., 2000).
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GHRP-1
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Research
Growth Hormone Release
In comparative studies, GHRP-1 stimulates GH release from pituitary somatotrophs but with lower potency than GHRP-2 and GHRP-6. Bowers et al. demonstrated that structural modifications to the hexapeptide backbone could dramatically alter potency and selectivity, with GHRP-1 serving as the foundational scaffold from which more potent analogs were developed (Bowers et al., 1994). The peptide produces dose-dependent GH elevation with associated increases in cortisol and prolactin at higher doses.
Cardioprotection
Research in fetal heart cell cultures demonstrated that GHRP-1, along with GHRP-2 and GHRP-6, protects cardiomyocytes from apoptosis. This cardioprotective effect appears to be mediated through GHS-R1a signaling and is shared across the GHRP family, suggesting a conserved mechanism of cardiac cell survival independent of GH release (Muccioli et al., 2000).
Synergy with GHRH
Like other GHRPs, GHRP-1 demonstrates synergistic GH release when co-administered with GHRH or its analogs. Because GHRPs and GHRH activate distinct receptor pathways on somatotroph cells, the combined stimulus produces GH pulses 3-10 times greater than either agent alone. This synergy was first characterized using GHRP-1-class peptides and became a defining principle of growth hormone secretagogue pharmacology (Bowers, 1998).
Historical Discovery and GHS-R1a Identification
Cyril Bowers' systematic work with growth hormone releasing peptides throughout the 1980s and 1990s established the existence of a novel GH secretory pathway. GHRP-1 and its analogs demonstrated GH release that could not be explained by GHRH receptor activation, leading to the hypothesis and eventual cloning of the GHS-R1a receptor in 1996 by Howard et al. The subsequent identification of ghrelin as the endogenous GHS-R1a ligand in 1999 by Kojima et al. represented one of the most significant discoveries in endocrinology, connecting appetite, energy metabolism, and growth hormone regulation through a single receptor system (Bowers, 1998).
Safety Profile
GHRP-1 shares the general safety profile of growth hormone secretagogues. At standard research doses, it produces transient elevations in cortisol and prolactin that are dose-dependent and generally within physiological ranges. As with all GHS-R1a agonists, appetite stimulation and mild water retention may occur. GHRP-1 has been less extensively studied than GHRP-2 and GHRP-6, and comprehensive human safety data are limited. No serious adverse effects have been reported in published research at standard dosing.
Clinical Research Protocols
GHRP-1 has primarily been used in early investigational studies characterizing the GHS-R1a pathway rather than in formal clinical trials. Bowers and colleagues administered GHRP-1 intravenously at doses ranging from 0.1 to 1.0 mcg/kg in healthy volunteers, measuring serial GH, cortisol, and prolactin levels at 15-minute intervals for 60-90 minutes post-injection. These protocols established the dose-response characteristics and hormonal side-effect profile that guided development of subsequent GHRPs (Bowers et al., 1994). GHRP-1 was largely superseded by GHRP-2 for diagnostic applications due to the latter's greater potency and selectivity.
Synergies & Combinations
The primary documented synergy for GHRP-1 is with GHRH and its analogs. Co-administration produces synergistic rather than additive GH release, a property conserved across all GHRPs. In practice, GHRP-2 or ipamorelin have replaced GHRP-1 in combination protocols due to superior potency and selectivity. The GHRP + GHRH synergy principle first demonstrated with GHRP-1-class peptides remains the foundation of modern GH secretagogue combination research (Bowers, 1998).
Pharmacokinetic Profile
GHRP-1 — Pharmacokinetic Curve
Subcutaneous injection, IntravenousQuick Start
- Route
- Subcutaneous injection, Intravenous
Molecular Structure
- Formula
- C51H62N12O7
- Weight
- 955.1 Da
- CAS
- 142033-37-0
- PubChem CID
- 10350910
- Exact Mass
- 954.4864 Da
- LogP
- 2.8
- TPSA
- 314 Ų
- H-Bond Donors
- 11
- H-Bond Acceptors
- 10
- Rotatable Bonds
- 25
- Complexity
- 1750
Identifiers (SMILES, InChI)
InChI=1S/C51H62N12O7/c1-30(53)46(65)60-44(26-37-28-55-29-57-37)51(70)63-42(24-33-19-20-34-14-6-7-15-35(34)22-33)48(67)58-31(2)47(66)61-43(25-36-27-56-39-17-9-8-16-38(36)39)50(69)62-41(23-32-12-4-3-5-13-32)49(68)59-40(45(54)64)18-10-11-21-52/h3-9,12-17,19-20,22,27-31,40-44,56H,10-11,18,21,23-26,52-53H2,1-2H3,(H2,54,64)(H,55,57)(H,58,67)(H,59,68)(H,60,65)(H,61,66)(H,62,69)(H,63,70)/t30-,31-,40-,41+,42+,43-,44-/m0/s1
NWQWNCILOXTTHF-HLCSKTDOSA-NResearch Protocols
intravenous Injection
Bowers and colleagues administered GHRP-1 intravenously at doses ranging from 0.1 to 1.0 mcg/kg in healthy volunteers, measuring serial GH, cortisol, and prolactin levels at 15-minute intervals for 60-90 minutes post-injection.
| Goal | Dose | Frequency | Duration |
|---|---|---|---|
| General Research Protocol | 1.0 mcg | Per protocol | —(Route: Intravenous Injection) |
subcutaneous Injection
Administered via subcutaneous injection.
Interactions
Peptide Interactions
Like other GHRPs, GHRP-1 demonstrates synergistic GH release when co-administered with GHRH or its analogs. Because GHRPs and GHRH activate distinct receptor pathways on somatotroph cells, the combined stimulus produces GH pulses 3-10 times greater than either agent alone. This synergy was first ...
In practice, GHRP-2 or ipamorelin have replaced GHRP-1 in combination protocols due to superior potency and selectivity.
GHRP-1 is less commonly used in contemporary research compared to GHRP-2 and GHRP-6, which offer greater potency and better-characterized pharmacology.
GHRP-1 is less commonly used in contemporary research compared to GHRP-2 and GHRP-6, which offer greater potency and better-characterized pharmacology.
This work ultimately established an entirely new axis of GH regulation alongside GHRH and somatostatin.
Quality Indicators
What to look for
- Multiple peer-reviewed studies available
Red flags
- Significant side effect risk noted
Frequently Asked Questions
References (7)
- [7]
- [8]Muccioli et al -- Growth hormone-releasing peptides and the cardiovascular system Ann Endocrinol (2000)
- [1]Bowers CY *Cell Mol Life Sci* Cell Mol Life Sci (1998)
- [2]Bowers CY et al *Endocrinology* Endocrinology (1994)
- [3]Muccioli et al *Ann Endocrinol* Ann Endocrinol (2000)
- [5]Howard et al *Science* Science (1996)
- [6]Kojima et al *Nature* Nature (1999)
GHRH (Growth Hormone Releasing Hormone)
GHRH is a 44-amino acid endogenous hypothalamic peptide that stimulates pulsatile growth hormone release from the anterior pituitary. It is the primary physiological regulator of GH secretion and the parent molecule from which synthetic analogues like sermorelin and CJC-1295 are derived.
GHRP-2
GHRP-2 (pralmorelin) is a synthetic growth hormone secretagogue that binds the ghrelin receptor, with research applications in muscle preservation, appetite regulation, immune function, sleep quality, and pain modulation.