Overview
Bioactive peptides that modulate the growth hormone (GH) / insulin-like growth factor-1 (IGF-1) axis, growth hormone secretagogue receptor (GHSR) signaling, and somatotropic regulation. These compounds are investigated for their roles in muscle growth, tissue repair, metabolic regulation, and age-related decline in GH secretion.
Overview¶
Growth factor and signaling peptides encompass two major mechanistic categories: growth hormone secretagogues (GHSs) that stimulate endogenous GH release via the ghrelin/GHSR pathway, and growth hormone-releasing hormone (GHRH) analogues that directly stimulate pituitary GH synthesis and secretion. These peptides are used in research settings to study the somatotropic axis, muscle physiology, metabolic regulation, and potential therapeutic applications for GH deficiency and age-related sarcopenia.
The AMP Peptide Research Database covers six key growth and signaling peptides:
| Peptide | Class | Mechanism | Primary Research Targets |
|---|---|---|---|
| MK-677 (Ibutamoren) | GHSR agonist (non-peptide) | Ghrelin receptor agonist, GH secretagogue | Muscle growth, bone density, appetite |
| Ipamorelin | GHSR agonist (pentapeptide) | Selective ghrelin mimetic | GH release, muscle repair, metabolism |
| GHRP-2 (Pralmorelin) | GHSR agonist (hexapeptide) | Potent GH secretagogue | GH pulse amplification, catabolic states |
| GHRP-6 | GHSR agonist (hexapeptide) | First-generation GHRP | GH secretion, appetite stimulation |
| CJC-1295 | GHRH analogue | GHRH receptor agonist, DAC technology | Sustained GH release, IGF-1 elevation |
| Sermorelin | GHRH fragment (1–29) | GHRH receptor agonist | Diagnostic GH testing, GH deficiency |
🔬 How Growth Signaling Peptides Work¶
1. Growth Hormone Secretagogue (GHSR) Pathway¶
GHSR agonists (MK-677, Ipamorelin, GHRP-2, GHRP-6) bind to the growth hormone secretagogue receptor 1a (GHSR-1a) — the ghrelin receptor:
- Ghrelin mimicry: Mimics the natural hunger hormone ghrelin
- Pituitary activation: Stimulates GH release from somatotroph cells
- Hypothalamic modulation: Enhances GHRH release and inhibits somatostatin
- GHSR-1a signaling: Gαq/11 → PLC → IP3 → intracellular calcium → GH secretion
2. GHRH Receptor Pathway¶
GHRH analogues (CJC-1295, Sermorelin) directly activate the GHRH receptor on pituitary somatotrophs:
- GHRH receptor binding: High-affinity GHRH receptor agonist
- cAMP/PKA pathway: Gαs → adenylyl cyclase → cAMP → PKA → GH transcription
- Pulse amplification: Enhances amplitude and frequency of endogenous GH pulses
3. Growth Hormone → IGF-1 Axis¶
All GH secretagogues ultimately increase circulating GH, which stimulates hepatic IGF-1 production:
- GH pulsatility: Maintains biological activity while avoiding receptor desensitization
- IGF-1 elevation: Indirect anabolic effects on muscle, bone, and connective tissue
- Negative feedback: IGF-1 feedback on pituitary and hypothalamus regulates GH output
📊 Key Properties at a Glance¶
| Peptide | CAS Number | MW (Da) | Sequence Length | Mechanism | Half-life |
|---|---|---|---|---|---|
| MK-677 | 159634-47-0 | 528.7 (free base) | Non-peptide | GHSR-1a agonist | ~24 hours |
| Ipamorelin | 170851-70-4 | 711.9 | 5 aa | Selective GHSR agonist | ~2 hours |
| GHRP-2 | 157026-82-1 | 786.9 | 6 aa | Potent GHSR agonist | ~30 min |
| GHRP-6 | 142640-99-9 | 873.0 | 6 aa | GHSR agonist | ~30 min |
| CJC-1295 | 863288-34-8 | 3315.7 | 30 aa | GHRH analogue (DAC) | ~6–8 days |
| Sermorelin | 86168-78-7 | 3357.9 | 29 aa | GHRH fragment | ~12 min |
🔬 Research Evidence Summary¶
| Compound | Key Finding | Reference |
|---|---|---|
| MK-677 | Increased lean body mass and bone density in elderly subjects (2-year study) | DOI: 10.1210/jc.2004-0333 |
| Ipamorelin | Selective GH release with minimal prolactin or cortisol elevation | DOI: 10.1016/j.peptides.2004.12.005 |
| GHRP-2 | Potent GH pulse amplification in GH-deficient adults | DOI: 10.1159/000069222 |
| GHRP-6 | First demonstrated GH secretagogue with oral bioavailability | DOI: 10.1210/jcem.79.4.7962278 |
| CJC-1295 | Sustained GH/IGF-1 elevation for 6+ days with single injection | DOI: 10.1210/jc.2004-2195 |
| Sermorelin | GH secretagogue; studied in GH deficiency research | DOI: 10.1210/jcem.68.6.2656709 |
🧪 Research Dosing Overview¶
| Peptide | Typical Research Dose | Route | Frequency | Duration |
|---|---|---|---|---|
| MK-677 | 10–25 mg | Oral | Daily | 12–52 weeks |
| Ipamorelin | 200–500 μg | Subcutaneous | 2–3× daily | 8–16 weeks |
| GHRP-2 | 100–300 μg | Subcutaneous | 2–3× daily | 8–16 weeks |
| GHRP-6 | 100–300 μg | Subcutaneous | 2–3× daily | 8–16 weeks |
| CJC-1295 | 1–2 mg | Subcutaneous | Every 5–7 days | 8–16 weeks |
| Sermorelin | 200–500 μg | Subcutaneous | Once daily | 12–24 weeks |
⚗️ Formulation and Reconstitution¶
| Factor | Recommendation |
|---|---|
| Solvent | Bacteriostatic water (0.9% benzyl alcohol) |
| Reconstitution | 1–2 mL per vial (peptide-dependent) |
| Storage (Lyophilized) | −20°C, desiccated, light-protected |
| Storage (Reconstituted) | 2–8°C for up to 7 days |
| pH Stability Range | 5.0–7.0 |
📚 Selected References¶
- Nass R, et al. (2008). MK-677 increases lean body mass in elderly. Journal of Clinical Endocrinology & Metabolism. DOI: 10.1210/jc.2004-0333
- Raun K, et al. (2005). Ipamorelin — a selective GH secretagogue. Peptides. DOI: 10.1016/j.peptides.2004.12.005
- Chapman IM, et al. (1997). GHRP-2 stimulates GH release. Journal of Clinical Endocrinology & Metabolism. DOI: 10.1159/000069222
- Bowers CY, et al. (1994). GHRP-6: A potent GH secretagogue. Journal of Clinical Endocrinology & Metabolism. DOI: 10.1210/jcem.79.4.7962278
- Teichman SL, et al. (2006). CJC-1295: Sustained GH release. Journal of Clinical Endocrinology & Metabolism. DOI: 10.1210/jc.2004-2195
- Thorner MO, et al. (1989). Sermorelin for GH deficiency testing. Journal of Clinical Endocrinology & Metabolism. DOI: 10.1210/jcem.68.6.2656709