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Sermorelin

GHRH 1-29 · Geref · Growth Hormone Releasing Peptide

A 29-amino-acid peptide corresponding to the first 29 residues of natural GHRH (1-44). The shortest fragment that retains full biological activity. FDA-approved as a diagnostic agent for GH deficiency and formerly approved for GH-deficient children.

29 amino acids
GHRH 1-29 fragment
FDA approved (diagnostic)
Natural sequence
First GHRH therapeutic
Educational content only. Not medical advice. This peptide may not be FDA-approved. Full disclaimer →
Category
GH Releasing
Route
SC / IV injection
Half-life
~10-20 minutes
Approval
FDA (diagnostic)
Evidence
Clinical

What Is Sermorelin?

Sermorelin (GHRH 1-29) is a 29-amino-acid peptide that is the biologically active fragment of the 44-amino-acid growth hormone-releasing hormone. It was the first GHRH-based therapeutic developed, demonstrating that only the first 29 residues are needed for full GHRH receptor activation.

Unlike exogenous GH injection, sermorelin stimulates the pituitary to produce and release its own GH through the natural GHRH receptor pathway. This preserves the physiological pulsatile pattern of GH secretion and allows the body's feedback mechanisms to prevent excess GH levels.

Core Concept
Sermorelin binds the GHRH receptor (a Gs-coupled GPCR) on anterior pituitary somatotrophs, activating adenylyl cyclase and increasing cAMP, which triggers GH gene transcription and granule release. Its short half-life (~10-20 min) means it produces a GH pulse similar to natural GHRH, but it requires frequent dosing. CJC-1295 was developed specifically to solve this half-life limitation.

Structure & Sequence

Sermorelin
YADAIFTNSYRKVLGQLSARKLLQDIMSRN
MW: 3,357.9 Da · 29 residues
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Mechanism of Action

Sermorelin is the prototypical GHRH receptor agonist. It activates the same Gs-cAMP-PKA cascade as native GHRH, stimulating both GH gene transcription and release of stored GH granules from somatotrophs.

Sermorelin GH Stimulation
Binds
GHRH receptor
Activates
Gs → cAMP → PKA
Stimulates
GH synthesis + release
Pituitary
pulses GH naturally
Result
Growth + Repair

Key Mechanisms

PathwayEffectSignificance
GHRH-R agonismFull activation of GHRH receptor with first 29 residuesIdentical signaling to native GHRH 1-44
Pulsatile GHShort half-life produces natural GH pulsesPreserves physiological GH secretion pattern
IGF-1 stimulationGH-mediated hepatic IGF-1 productionDownstream growth, repair, and metabolic effects
No GH suppressionWorks through natural axis, not exogenous replacementBody's feedback prevents excess GH

Evidence Base

StudyDesignFindingsLevel
GH deficiency diagnosisFDA-approved diagnosticIV sermorelin measures pituitary GH reserve. Normal response rules out pituitary cause of GH deficiency.Level I
Pediatric GH deficiencyFormer FDA indicationStimulated growth in GH-deficient children. Withdrawn from market (2008) for commercial reasons, not safety.Level I
Anti-agingClinical studiesIncreased IGF-1, improved body composition, sleep quality in adults. Off-label use common.Level II-III

Safety & Side Effects

Well-tolerated: Injection site reactions, facial flushing, headache most common. Generally mild.

Short duration: Requires daily injection due to short half-life. Less convenient than CJC-1295.

Regulatory Status

JurisdictionStatus
FDAApproved as diagnostic (Geref). Former therapeutic approval withdrawn 2008 (commercial, not safety).
WADABanned under S2
StatusLargely replaced by CJC-1295 and tesamorelin in clinical use

Sermorelin vs CJC-1295

FeatureSermorelinCJC-1295
Length29 amino acids30 amino acids
Half-life10-20 minutes6-8 days (with DAC)
DosingDaily injectionWeekly injection
ModificationNone (natural sequence)DAC for albumin binding
FDA statusApproved (diagnostic)Not approved

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