Sermorelin

Sermorelin is a synthetic 29-amino-acid peptide identical in sequence to residues 1–29 of native human growth-hormone-releasing hormone (GHRH) — the minimum N-terminal fragment retaining full pituitary GH-secretagogue activity. Among the GHRH-analog research catalogue, sermorelin is the most physiologically faithful: no enzymatic stabilisation, no albumin tether, and the resulting GH-release pattern remains subject to normal somatostatin-mediated negative feedback (Pedrolli et al. 2026, PMID 41946684; Mendias et al. 2026, PMID 41966639).

Sermorelin has the longest US human-clinical track record of any GHRH analog. Serono received FDA approval for sermorelin acetate (Geref) in 1997 for diagnosis and management of pediatric idiopathic growth-hormone deficiency. Marketing was discontinued in 2008 for commercial — not safety — reasons. Sermorelin was placed on the FDA’s interim 503A bulks Category 2 in September 2023 and removed from Category 2 on 27 September 2024 (Federal Register document 2024-24828); it remains under PCAC review as of 2026 and is not currently FDA-approved.

A new 2026 mechanism finding (Pedrolli et al., Cell Death & Disease, PMID 41946684) reports that GHRH-receptor agonism reduces amyloid-β deposition, suppresses glial activation, and lowers pro-inflammatory cytokine expression in the 5xFAD transgenic Alzheimer’s-disease mouse model — opening an emerging neuroprotective research direction for the GHRH-analog class. This is preclinical work and does not constitute a therapeutic claim.

Each Artemis Labs vial ships with a third-party Certificate of Analysis confirming identity (mass spectrometry), purity (≥99% by reverse-phase HPLC), and endotoxin testing (LAL assay, ≤0.5 EU/mg). Sermorelin is prohibited at all times under WADA Section S2 (Peptide Hormones, Growth Factors, Related Substances and Mimetics; Coutinho et al. 2026, PMID 41880199). For laboratory research use only — no human dosing, administration, therapeutic, diagnostic, or preventative claim is made.

Science & Research

## Mechanism of Action

Sermorelin binds the GHRH receptor (GHRH-R), a Class-B GPCR expressed on anterior-pituitary somatotrophs. Receptor activation drives Gαs / cAMP / PKA signalling, increasing GH gene transcription and pulsatile vesicular exocytosis. Because the sermorelin sequence is identical to endogenous human GHRH(1-29), the resulting GH-release pattern is the most physiologically faithful of any GHRH analog in research use and remains subject to normal somatostatin-mediated negative feedback (Pedrolli 2026, PMID 41946684; Mendias 2026, PMID 41966639).

## Pharmacokinetic Profile (Published Research)

– Plasma half-life: ~10–20 minutes; no enzymatic stabilisation, no albumin tether
– Time-to-peak plasma: ~5–20 minutes post-subcutaneous administration (published-research context)
– GH-pulse duration: GH elevation persists ~3 hours despite rapid peptide clearance, reflecting downstream somatotroph kinetics
– Bioavailability: subcutaneous is the standard published route; intranasal bioavailability is ~3–5%; oral bioavailability is negligible

## New 2026 Mechanism Finding — Neuroprotective Research Direction

Pedrolli et al. 2026 (Cell Death & Disease, PMID 41946684) reported that GHRH(1-44) and the GHRH agonist MR-409 reduce amyloid-β deposition, suppress gliosis, and lower pro-inflammatory cytokine expression in the 5xFAD transgenic Alzheimer’s-disease mouse model. The work establishes a preclinical case that GHRH-receptor agonism has consequential signalling beyond pituitary GH release — an emerging neuroprotective research direction for the GHRH-analog class. This is preclinical research and does not constitute a therapeutic claim.

## Receptor-Pathway Context (GHRH-R Antagonist Class)

Independent 2024–2025 work characterised GHRH-receptor antagonists (MIA-602, MIA-690) as showing anti-tumour activity through autophagy induction and chemo-/radio-sensitisation across multiple cancer cell models (Sigdel 2025, PMID 41075421; Gesmundo 2025, PMID 40244089; Muñoz-Moreno 2024, PMID 39456984; Costoya 2025, PMID 39417961; Gaumond 2024, PMID 38588464). These are antagonist (opposite-pharmacology) findings — they are included as receptor-pathway context demonstrating the GHRH-R’s biological breadth, not as sermorelin findings.

## Regulatory History (1997–2026)

– 1997 — FDA approval (Geref). Serono received FDA approval for sermorelin acetate (Geref) for diagnosis and management of pediatric idiopathic GH deficiency.
– 2008 — Marketing discontinued. Serono / Merck Serono discontinued commercial marketing of Geref for business reasons; not driven by safety concerns. Sermorelin retains the longest human-clinical track record of any GHRH analog (Mendias 2026, PMID 41966639).
– September 2023 — FDA 503A Category 2 placement (alongside CJC-1295 and ipamorelin).
– 27 September 2024 — Category 2 removal following nominator withdrawal (Federal Register document 2024-24828).
– Current (2026) — Not on FDA positive bulks list; not currently FDA-approved; under PCAC review.
– WADA Prohibited List — Section S2 (Peptide Hormones, Growth Factors, Related Substances and Mimetics), prohibited at all times (Coutinho 2026, PMID 41880199).

## Specifications

| Property | Value |
|—|—|
| Sequence | YADAIFTNSYRKVLGQLSARKLLQDIMSR-NH₂ (GHRH residues 1–29) |
| Molecular Formula | C₁₄₉H₂₄₆N₄₄O₄₂S |
| Molecular Weight | 3,357.9 g/mol (free base) |
| CAS Number | 86168-78-7 |
| Purity Standard | ≥99% by reverse-phase HPLC (lot-specific COA) |
| Storage (lyophilised) | Store at −20 °C, desiccated, protected from light |
| Endotoxin | Tested ≤ 0.5 EU/mg (LAL assay; lot-specific) |
| Form | Lyophilised white acetate-salt powder; 5 mg or 10 mg vial |

## Key Citations (selection)

1. Pedrolli F. 2026. *Cell Death Dis.* — GHRH attenuates amyloid deposition + neuroinflammation in 5xFAD AD models. PMID 41946684.
2. Mendias CL, Awan TM. 2026. *Sports Med.* — Approved + unapproved peptide therapies for musculoskeletal injuries + athletic performance. PMID 41966639.
3. Coutinho LFD et al. 2026. *J Sports Med Phys Fitness.* — Peptide & peptide-analog drugs in recreational + professional sport (anti-doping context). PMID 41880199.
4. Rahman OF et al. 2026. *J Am Acad Orthop Surg Glob Res Rev.* — Therapeutic peptides in orthopaedics review. PMID 41490200.
5. Uçaktürk E, Nemutlu E. 2026. *J Pharm Biomed Anal.* — Nano-LC + Q/Orbitrap MS analysis of GHRH and analogs in urine. PMID 41138283.
6. Federal Register. 2024-10-25. PCAC Notice of Meeting (Document 2024-24828) — Category 2 removal for sermorelin.

Full citations + GHRH-R antagonist-class context: see Artemis Labs sermorelin research page.

**No dosing, frequency, route, or human-protocol guidance is supplied. For laboratory research use only.**

Research-Design Pairings

## Research-Design Pairings (Not Human Protocols)

In published research, GHRH agonists such as sermorelin are studied alongside GHS-R1a agonists (ipamorelin) because the two receptor pathways converge on somatotroph GH release through different intracellular cascades (Mavrych et al. 2026, PMID 42021992). Pairings below are *research-design rationale*, not human-protocol recommendations.

### Sermorelin + Ipamorelin (orthogonal-receptor research pairing)

– **Sermorelin** — GHRH-R agonist, native GHRH(1-29) sequence; physiologically faithful Gαs / cAMP / PKA signal
– **Ipamorelin** — GHS-R1a agonist (ghrelin-receptor class); different receptor, complementary intracellular cascade
– **Why studied together** — receptor-class orthogonality enables dissection of pathway-specific contributions to somatotroph GH release; convergent endpoint (GH pulse) with divergent upstream pharmacology

### Sermorelin vs CJC-1295 (kinetic comparator pairing)

– **Sermorelin** — native sequence, no enzymatic stabilisation, ~10–20 min plasma half-life
– **CJC-1295 with DAC** — modified GHRH analog with MPA-Lys albumin handle; half-life 6–8 days
– **Why studied together** — comparator pair for kinetic-modulation studies; isolates the effect of half-life extension while holding receptor target constant

### Sermorelin vs Tesamorelin (regulatory + structure comparator)

– **Sermorelin** — native GHRH(1-29); not currently FDA-approved
– **Tesamorelin** — trans-3-hexenoyl GHRH(1-44); the only currently FDA-approved GHRH analog (Egrifta SV / Egrifta WR, HIV-associated lipodystrophy indication)
– **Why studied together** — benchmark for safety/efficacy data when designing research protocols against the approved-comparator standard

### MOTS-c (downstream metabolic context)

– **MOTS-c** — mitochondrial-derived peptide; co-studied for downstream metabolic effects in GH-axis research designs

**No dosing, frequency, route, or human-protocol guidance is supplied.** Stacking commentary above is restricted to in-vitro and pre-clinical research-design rationale per CLAUDE.md content rule #1.

For mechanism-level deep-dive, see the [sermorelin research page](https://artemispeptides.com/product/sermorelin/) (Science & Research tab + full citation list).