Sermorelin
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GHRH(1-29) analog identical to the first 29 amino acids of native growth hormone-releasing hormone, stimulating pituitary GH production while preserving natural pulsatile rhythm.
Quick Facts
| Property | Value |
|---|---|
| Also Known As | Sermorelin Acetate, GRF 1-29, GHRH(1-29)NH2, Geref (withdrawn brand) |
| Category | GH Axis / Anti-Aging / Sleep |
| Sequence | Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-NH2 (29 AA) |
| Molecular Weight | 3357.9 Da |
| Molecular Formula | C149H246N44O42S |
| PubChem CID | 16129620 |
| Administration | SubQ (traditional), Oral (capsule formulation available) |
| Typical Dose Range | 0.2-0.3 mg/day SubQ; 500 mcg oral |
| Half-Life | ~10-20 minutes |
| Storage | Lyophilized: -20C long-term; 2-8C up to 3 months. Reconstituted: 2-8C for 3-4 weeks |
| FDA Status | Previously FDA-approved (Geref Diagnostic, withdrawn 2008 — manufacturing issues, not safety) |
| WADA Status | Prohibited S2 (Peptide Hormones, Growth Factors) |
Mechanism of Action
Sermorelin is the oldest clinically used GH secretagogue, comprising the biologically active N-terminal 29 amino acids of native 44-amino acid GHRH. It binds the GHRH receptor (GHRH-R) on anterior pituitary somatotroph cells, activating adenylyl cyclase via Gs-protein coupling. This increases intracellular cAMP, activates protein kinase A (PKA), and stimulates both GH (GH1, UniProt P01241) gene transcription and GH vesicle exocytosis (PMID: 18031173).
Unlike exogenous recombinant GH, sermorelin preserves the physiological pulsatile GH release pattern because somatostatin feedback remains intact. This creates a self-limiting "safety net" — GH levels cannot rise to dangerous levels because the normal hypothalamic feedback loop suppresses excess release (PMID: 18046908). This is the primary clinical advantage of GHRH analogs over direct GH replacement.
The short half-life (~10-20 minutes, PMID: 8329825) explains why bedtime dosing is preferred: the brief stimulation aligns with the natural nocturnal GHRH surge that drives sleep-associated GH release. GH secretion during slow-wave sleep is amplified, improving both sleep architecture and GH output simultaneously.
In aging adults, 5-month GHRH(1-29) administration significantly increased 24-hour GH secretion and IGF-1 levels, with lean body mass increases in men and skin thickness improvements in both genders (PMID: 9141536). Immunological benefits were also documented, including increased NK cell activity and IL-2 production (PMID: 9360512).
Key Research Areas
- Anti-aging GH restoration — Restores GH-IGF-1 axis in age-related decline without GH excess risk (PMID: 9141536, 18046908)
- Pediatric GH deficiency — Previously FDA-approved for diagnosis and treatment of idiopathic GHD (PMID: 18031173)
- Immune reconstitution — Increased NK cells, IL-2, and CD4+ T cells in aging adults (PMID: 9360512)
- Body composition — Lean mass improvement and skin quality enhancement in elderly
- Sleep quality — Amplification of slow-wave sleep via nocturnal GH pulse enhancement
- Pharmacokinetics — IV and intranasal PK characterization (PMID: 8329825)
Evidence Level Summary
| Evidence Type | Count | Notes |
|---|---|---|
| Human RCTs | 3 | Aging body composition, immune effects, PK study |
| Human observational | 1+ | Clinical use data from Geref era |
| Animal in vivo | Multiple | Extensive GH axis pharmacology |
| In vitro | Multiple | Receptor binding, signaling |
| Systematic reviews | 1 | BioDrugs review of pediatric use (PMID: 18031173) |
Clinical Applications
- Anti-Aging — GH axis restoration in age-related decline
- Sarcopenia — Lean mass improvement via GH/IGF-1 support
- Sleep Disorders — Slow-wave sleep enhancement
- Immune Support — NK cell and T-cell immune reconstitution
- Fat Loss — Body composition improvement via GH axis
- Bone Density — IGF-1-mediated bone metabolism support
- Recovery — Tissue repair via GH/IGF-1 signaling
Protocols Using This Peptide
Ageless Peps Products
- AP-Sermorelin-Vial — Sermorelin Vial, $44, retail (draft status)
- AP-Sermorelin-Capsules — Sermorelin 500mcg x 60 capsules, $154
Dosing Reference
Research Dosing Ranges (from literature)
| Route | Dose Range | Frequency | Duration | Source |
|---|---|---|---|---|
| SubQ | 0.2-0.3 mg | Once daily (bedtime) | 3-6 months | Clinical practice / Geref labeling |
| SubQ | 10 mcg/kg | Once daily (bedtime) | 5 months | PMID 9141536 (aging study) |
| SubQ | 30 mcg/kg | Once daily | Ongoing | PMID 18031173 (pediatric GHD) |
| IV | 1 mcg/kg | Single dose | Diagnostic | PMID 8329825 (GHD testing) |
| Oral | 500 mcg | Once daily (bedtime) | Ongoing | AP capsule formulation |
Cycling
Often used continuously for anti-aging; some practitioners recommend 5 days on / 2 days off or 3 months on / 1 month off to prevent tachyphylaxis. The short half-life means GH levels normalize within hours of stopping. No significant withdrawal or rebound effects expected.
Contraindications & Safety
- Contraindications: Active malignancy, acromegaly, pituitary tumors, diabetic retinopathy
- Common side effects: Facial flushing (transient), injection site redness/swelling, headache, dizziness
- Drug interactions: Glucocorticoids may blunt GH response; hypothyroidism reduces efficacy (correct thyroid first)
- Pregnancy/nursing: Contraindicated
- Special populations: Obesity reduces GH response to GHRH; elderly have naturally blunted response. Monitor IGF-1 levels. Unlike exogenous GH, does not suppress endogenous GH production.
Synergistic Combinations
- Ipamorelin + Sermorelin — GHRH + GHRP dual stimulation for synergistic GH pulse amplification
- GHRP-2 + Sermorelin — Classic GHRH + GHRP combination; more potent than Ipamorelin pairing but more side effects
- CJC-1295 NO DAC + Sermorelin — Alternative GHRH; typically used as either/or rather than combined
- Epitalon + Sermorelin — Anti-aging stack: GH axis + telomerase activation
Related Research
| PMID | Title | Year | Study Type |
|---|---|---|---|
| PMID-9141536 – Sermorelin Long-Term GHRH in Age-Advanced Adults | Long-term GHRH administration in age-advanced adults | 1997 | RCT |
| PMID-18046908 – Sermorelin Better Approach to Adult GH Insufficiency | Sermorelin: better approach to adult GH insufficiency | 2006 | Narrative Review |
| PMID-18031173 – Sermorelin Review Diagnosis and Treatment GHD | Sermorelin review for diagnosis and treatment of GHD | 2007 | Systematic Review |
| PMID-9360512 – Sermorelin GHRH Immune System Effects in Aging | GHRH immune system effects in aging | 1997 | RCT |
| PMID-8329825 – Sermorelin PK and GH Secretion IV vs Intranasal | Sermorelin PK and GH secretion IV vs intranasal | 1993 | RCT |
References
- PMID 9141536 — Khorram et al., JCEM 1997 (anti-aging RCT)
- PMID 18046908 — Walker, Clin Interv Aging 2006 (clinical review)
- PMID 18031173 — Kemp & Fielder, BioDrugs 2007 (systematic review)
- PMID 9360512 — Khorram et al., JCEM 1997 (immune effects)
- PMID 8329825 — Evans et al., JCEM 1993 (PK study)
Related
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