≥99%HPLC Purity
COAIncluded
USAShipped
GHRP-6 Peptide
Growth Hormone Releasing Peptide-6 is a synthetic hexapeptide GHS-R1a agonist. One of the earliest characterized growth hormone secretagogues.
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Quick Facts
| SKU | ACR-GHRP6 |
|---|---|
| CAS Number | 87616-84-0 |
| Molecular Formula | C46H56N12O6 |
| Molecular Weight | 873.01 g/mol |
| Sequence | His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 |
| Purity | ≥98% |
| Physical Form | Lyophilized Powder |
| Storage | Store at -20°C |
What is GHRP-6?
GHRP-6 (Growth Hormone Releasing Peptide-6) is a synthetic hexapeptide (His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) that acts as a potent growth hormone secretagogue. It was one of the first synthetic peptides identified to stimulate GH release through the GHS-R1a (ghrelin) receptor.
GHRP-6 activates the ghrelin receptor independently of the GHRH pathway. Published research has documented its GH-releasing potency and its additional effects on appetite stimulation and cortisol/prolactin modulation, which distinguish it from more selective GHS compounds like Ipamorelin.
For laboratory research use only.
Mechanism of Action
GHRP-6 (Growth Hormone Releasing Peptide-6) is a synthetic hexapeptide (His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) that functions as a selective agonist of the growth hormone secretagogue receptor type 1a (GHS-R1a). This G-protein coupled receptor was later identified as the endogenous receptor for ghrelin, making GHRP-6 one of the foundational tools in the discovery of the ghrelin/GHS-R signaling axis.
GHS-R1a Activation
Upon binding to GHS-R1a in the anterior pituitary and hypothalamus, GHRP-6 triggers Gq-coupled signaling, activating phospholipase C (PLC), which hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol trisphosphate (IP3) and diacylglycerol (DAG). The resulting increase in intracellular calcium drives somatotroph depolarization and growth hormone (GH) release. Reported EC50 values for GHRP-6 at GHS-R1a are in the low nanomolar range (~10 nM in heterologous expression systems).
Dual-Site Action: Pituitary and Hypothalamus
Unlike GHRH, which acts primarily on pituitary somatotrophs via the GHRH receptor (Gs/cAMP), GHRP-6 acts at two anatomical sites: it directly stimulates pituitary GH release and it activates hypothalamic neurons that suppress somatostatin tone while amplifying endogenous GHRH release. This dual mechanism produces synergistic GH pulses when GHRP-6 is co-administered with GHRH analogs such as CJC-1295 or sermorelin, an effect first characterized by Bowers and colleagues.
Appetite and Orexigenic Signaling
GHRP-6 robustly stimulates food intake in preclinical models through activation of GHS-R1a on neuropeptide Y (NPY) and agouti-related peptide (AgRP) neurons in the arcuate nucleus of the hypothalamus. This orexigenic signature distinguishes GHRP-6 from later-generation analogs such as ipamorelin, which were engineered to minimize appetite stimulation.
Secondary Effects on Cortisol and Prolactin
At supraphysiological doses, GHRP-6 produces modest increases in adrenocorticotropic hormone (ACTH), cortisol, and prolactin. These off-target effects are smaller than those of GHRP-2 and substantially larger than those of ipamorelin, which is essentially silent at the HPA axis in research models.
Research & Clinical Studies
Discovery and Characterization of GHS-R1a Using GHRP-6
The 1996 landmark paper by Howard et al., published in Science, used GHRP-6 as the pharmacological probe to clone and characterize the orphan G-protein coupled receptor that became known as GHS-R1a. This receptor was subsequently identified as the endogenous target of ghrelin in 1999, fundamentally reshaping understanding of GH regulation, appetite, and energy balance.
Study Design
- Expression cloning approach using a swine pituitary cDNA library
- Functional readout: aequorin-based calcium mobilization in HEK293 cells transfected with candidate receptors
- GHRP-6 used as the reference ligand for receptor identification and Bmax determination
Key Findings
- Identified a 366-amino-acid GPCR with seven transmembrane domains, expressed predominantly in the anterior pituitary and hypothalamus
- GHRP-6 produced concentration-dependent calcium mobilization with an EC50 of approximately 1-10 nM
- Receptor expression was confirmed in human, rat, and porcine pituitary tissue
- Provided the molecular framework for the subsequent identification of ghrelin (Kojima et al., 1999) as the endogenous ligand
Research Context
This study is foundational because it established that GHRPs do not act through the GHRH receptor — a long-standing question after GHRP-6 was first synthesized by Bowers in 1984. The discovery of GHS-R1a opened an entirely new field of ghrelin biology, including its roles in appetite, gastric motility, glucose homeostasis, and reward signaling.
[1] Howard AD, Feighner SD, Cully DF, et al. A receptor in pituitary and hypothalamus that functions in growth hormone release. Science. 1996;273(5277):974-977. PubMed ↗
[2] Kojima M, Hosoda H, Date Y, et al. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999;402(6762):656-660. PubMed ↗
GHRP-6 Synergy with GHRH on Growth Hormone Release
Bowers and colleagues demonstrated that GHRP-6 and GHRH act through distinct but complementary pathways, producing markedly synergistic GH release when co-administered. This work established the rationale for combining GHRPs with GHRH analogs in research protocols.
Study Design
- Healthy adult human subjects (research setting)
- IV bolus comparison of GHRH alone, GHRP-6 alone, and the combination
- Serial GH sampling over 120 minutes
Key Results
- GHRH alone produced a peak GH response of approximately 10-20 ng/mL
- GHRP-6 alone produced a peak GH response of approximately 20-40 ng/mL
- GHRH + GHRP-6 in combination produced a peak GH response exceeding 80-100 ng/mL — a clearly supra-additive (synergistic) response
- The combination was effective even in older subjects with reduced baseline GH pulsatility
Mechanistic Interpretation
The synergy arises because GHRH activates Gs/cAMP signaling in pituitary somatotrophs while GHRP-6 activates Gq/PLC signaling at the same cells, in addition to suppressing somatostatin tone at the hypothalamic level. The two converging signals amplify GH exocytosis beyond what either ligand achieves alone. This finding underpins the widespread use of GHRP/GHRH combinations (e.g., GHRP-6 + sermorelin, ipamorelin + CJC-1295) in subsequent secretagogue research.
[1] Bowers CY, Reynolds GA, Durham D, Barrera CM, Pezzoli SS, Thorner MO. Growth hormone (GH)-releasing peptide stimulates GH release in normal men and acts synergistically with GH-releasing hormone. J Clin Endocrinol Metab. 1990;70(4):975-982. PubMed ↗
Frequently Asked Questions
What is GHRP-6?
GHRP-6 is a synthetic hexapeptide GH secretagogue that activates the GHS-R1a (ghrelin) receptor. It stimulates GH release and also affects appetite, cortisol, and prolactin — making it less selective than Ipamorelin. For research use only.
How does GHRP-6 compare to GHRP-2?
Both are hexapeptide GHS-R1a agonists, but GHRP-2 shows higher GH-releasing potency and somewhat greater selectivity. GHRP-6 produces more pronounced appetite stimulation through ghrelin pathway activation. Both stimulate cortisol and prolactin to a greater extent than Ipamorelin.
What is the molecular weight and CAS number of GHRP-6?
GHRP-6 has a molecular weight of 873.01 g/mol and a molecular formula of C46H56N12O6. Its CAS registry number is 87616-84-0. The peptide consists of six amino acid residues with the sequence His-D-Trp-Ala-Trp-D-Phe-Lys-NH2, featuring a C-terminal amidation and two D-amino acid substitutions (D-Trp at position 2 and D-Phe at position 5) that confer enzymatic stability and high GHS-R1a affinity. AminoCore Research supplies GHRP-6 as a lyophilized powder at ≥98% HPLC purity with a certificate of analysis.
How does GHRP-6 compare to ipamorelin?
Both GHRP-6 and ipamorelin are GHS-R1a agonists that stimulate growth hormone release, but their selectivity profiles differ substantially. GHRP-6 (1984, Bowers) is one of the earliest characterized growth hormone secretagogues and produces strong GH release alongside notable orexigenic (appetite-stimulating) signaling and modest increases in cortisol, ACTH, and prolactin at higher doses. Ipamorelin (1998) was specifically engineered for GHS-R1a selectivity and is essentially silent at the HPA axis, producing minimal cortisol or prolactin elevation and little to no appetite stimulation. GHRP-6 is therefore favored in research models studying ghrelin/orexigenic signaling, while ipamorelin is preferred when isolated GH-axis activation is desired.
Why does GHRP-6 stimulate appetite in research models?
GHRP-6 stimulates appetite because GHS-R1a — its primary target — is the same receptor activated by endogenous ghrelin, the body's principal orexigenic hormone. Activation of GHS-R1a on neuropeptide Y (NPY) and agouti-related peptide (AgRP) neurons in the hypothalamic arcuate nucleus increases food-seeking behavior and caloric intake in rodent models. This orexigenic property made GHRP-6 a key pharmacological tool in the discovery of ghrelin biology in the late 1990s. Research has shown dose-dependent increases in food intake within 30-60 minutes of administration in preclinical studies.
How should GHRP-6 be stored?
Lyophilized GHRP-6 should be stored at -20°C for long-term stability, where it remains stable for 24+ months when kept dry and protected from light. Short-term storage at 2-8°C is acceptable for several weeks, and brief exposure to room temperature during transit does not compromise integrity. Once reconstituted in bacteriostatic or sterile water, GHRP-6 should be refrigerated at 2-8°C and used within approximately 14-21 days. Repeated freeze-thaw cycles of reconstituted solution should be avoided, as the tryptophan residues are susceptible to oxidative degradation. Always protect both lyophilized and reconstituted material from direct light.
For laboratory and research use only. Not intended for human or animal consumption. All product information is derived from published preclinical research and does not constitute medical advice or claims.