Sermorelin

What is Sermorelin?

Sermorelin is a growth hormone-releasing hormone (GHRH) analog consisting of the first 29 amino acids of the naturally occurring 44-amino acid GHRH sequence. It is one of the few growth hormone-related peptides that has been FDA-approved for clinical use, specifically for the diagnosis and treatment of growth hormone deficiency in children.

Also known as GHRH(1-29) or GRF(1-29), sermorelin stimulates the pituitary gland to produce and release growth hormone naturally, preserving the body's normal feedback mechanisms and pulsatile release patterns.

Note: Sermorelin has FDA approval for specific pediatric indications. Its use in adults is off-label. This information is for educational purposes.

Discovery and Development

Origins

Sermorelin was developed after the discovery of GHRH in 1982. Researchers found that the first 29 amino acids of GHRH contained all the biological activity needed to stimulate growth hormone release, leading to the development of this truncated analog.

Approval History

• 1982: GHRH isolated and characterized
• 1984: GRF(1-29) synthesized and studied
• 1997: FDA approves sermorelin (Geref) for diagnostic use
• 1999: FDA approves for treatment of growth hormone deficiency in children
• 2008: Geref discontinued by manufacturer (business reasons, not safety)
• Present: Available through compounding pharmacies and research suppliers

Clinical Use History

Sermorelin was successfully used for years as:

• Diagnostic tool for growth hormone deficiency
• Treatment for pediatric growth hormone deficiency
• Alternative to direct growth hormone therapy

Molecular Profile

Chemical Structure

Sermorelin is a 29-amino acid peptide with the 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

Key Molecular Data

Structural Significance

• Positions 1-29: Complete biological activity of full GHRH
• C-terminal amidation: Improves stability
• Native sequence: Identical to human GHRH(1-29)

Mechanism of Action

GHRH Receptor Activation

Sermorelin works by binding to GHRH receptors (GHRHR) on pituitary somatotrophs:

Signaling Cascade:

1. Binds GHRH receptor on pituitary cells
2. Activates G-protein (Gαs)
3. Stimulates adenylyl cyclase
4. Increases intracellular cAMP
5. Activates protein kinase A
6. Enhances GH gene transcription
7. Promotes GH synthesis and release

Physiological Effects

Preserved Feedback:

• Works within natural regulatory system
• Maintains pulsatile GH release
• Allows somatostatin suppression
• Preserves IGF-1 negative feedback

GH Release Pattern:

• Acute GH spike within 15-30 minutes
• Returns to baseline within 2-3 hours
• Mimics natural secretion pattern
• Multiple daily peaks possible

Downstream Effects

Once growth hormone is released:

• Liver produces IGF-1
• Local tissues produce IGF-1
• Metabolic effects occur
• Tissue repair and regeneration enhanced

Clinical Applications

FDA-Approved Uses

Growth Hormone Deficiency Diagnosis:

• Stimulation test for GH secretion
• Assesses pituitary reserve
• Helps distinguish types of GH deficiency

Treatment of Pediatric GH Deficiency:

• Alternative to synthetic GH
• For children with functional pituitary
• Used when pituitary can respond to GHRH

Off-Label and Research Uses

Adult Growth Hormone Deficiency:

• Alternative to synthetic GH therapy
• May be preferred for natural stimulation
• Used in anti-aging medicine

Research Applications:

• Body composition studies
• Sleep quality research
• Recovery and regeneration studies
• Anti-aging investigations

Comparison with Other Peptides

Sermorelin vs Synthetic HGH

Sermorelin vs CJC-1295

Sermorelin vs GHRP

Synergistic Combinations

Sermorelin + GHRP-6

Classic combination protocol:

Rationale:

• Sermorelin: Stimulates GH synthesis pathway
• GHRP-6: Amplifies GH release via different receptor
• Combined effect: Synergistic GH elevation

Sermorelin + Ipamorelin

Preferred combination for selectivity:

Benefits:

• Clean side effect profile (Ipamorelin selectivity)
• Natural GH stimulation (Sermorelin)
• Synergistic amplification
• Well-tolerated combination

Sermorelin + GHRP-2

Alternative combination:

• Strong GH release
• Moderate side effects
• Effective research protocol

Administration and Dosing

Routes

Subcutaneous Injection:

• Most common method
• Rapid absorption
• Peak levels in 15-30 minutes

Intranasal (Historical):

• Was available in some formulations
• Lower bioavailability
• Variable absorption

Research Protocols

Typical research protocols involve:

• Once daily to multiple daily dosing
• Evening/bedtime administration common
• Fasted state often preferred
• Combined with GHRP when synergy desired

Timing Considerations

Optimal Timing:

• Before bed (mimics natural nocturnal peak)
• Upon waking (morning pulse)
• Post-exercise (physiological timing)
• Fasted state (enhanced response)

Stability and Storage

Lyophilized Form

• Store at -20°C for long-term
• Stable at 2-8°C for weeks
• Protect from light
• Keep desiccated

Reconstitution

Procedure:

1. Use bacteriostatic water
2. Direct diluent gently against vial wall
3. Swirl gently—never shake
4. Allow complete dissolution

After Reconstitution:

• Store at 2-8°C
• Use within 3-4 weeks
• Protect from light
• Avoid freeze-thaw cycles

Safety and Side Effects

Common Side Effects

At Injection Site:

• Redness
• Swelling
• Itching
• Pain (usually mild)

Systemic:

• Flushing
• Headache
• Dizziness
• Transient hypotension

Less Common Effects

• Nausea
• Sleepiness
• Altered taste
• Hyperactivity (children)

Safety Profile

Clinical Trial Data:

• Generally well-tolerated in trials
• Most side effects mild and transient
• Serious adverse events rare
• Long-term safety data available from pediatric use

Considerations:

• Antibody formation possible with chronic use
• May reduce effectiveness over time in some patients
• Monitor for local reactions

Advantages of Sermorelin

Over Direct GH Administration

1. Preserves Feedback: Natural regulatory mechanisms maintained
2. Pulsatile Release: Mimics physiological patterns
3. Lower Cost: Generally less expensive than HGH
4. Reduced Risk: Lower risk of excess GH side effects
5. Natural Production: Stimulates body's own GH production
6. Tachyphylaxis Rare: Less tolerance development

Clinical Advantages

• Can be used diagnostically
• Historical FDA approval (provides safety data)
• Works with body's natural systems
• May be combined with GHRPs for enhanced effect

Regulatory Status

FDA Status

• Approved (1997-1999) for diagnostic use and pediatric GH deficiency
• Discontinued by original manufacturer (2008) for business reasons
• Available through compounding pharmacies
• Research use widely available

WADA Status

• Prohibited substance in sports
• Classified under S2 (Peptide Hormones, Growth Factors)
• Banned in-competition and out-of-competition

Availability

• Compounding pharmacies (prescription)
• Research chemical suppliers
• Various international sources

Frequently Asked Questions

Why was Geref discontinued?

The manufacturer (EMD Serono) discontinued Geref in 2008 for business reasons, not safety concerns. The product was profitable but the company chose to exit this market. The peptide remains available through compounding pharmacies.

Is sermorelin as effective as HGH?

Sermorelin stimulates natural GH production, so effectiveness depends on pituitary function. In individuals with functional pituitaries, it can effectively raise GH and IGF-1 levels, though the magnitude may be less than direct HGH administration.

How quickly does sermorelin work?

Acute GH release occurs within 15-30 minutes of administration. For therapeutic effects like body composition changes, several weeks to months of consistent use are typically studied.

Can sermorelin be used with fasting?

Yes, sermorelin is often administered in a fasted state, which may enhance GH response. This is because food intake, particularly glucose, can blunt GH release.

Does sermorelin cause shutdown of natural GH?

No. Unlike direct HGH administration, sermorelin works through the body's natural GHRH receptor and preserves feedback mechanisms. It stimulates rather than replaces natural production.

Key Research References

1. Thorner, M.O., et al. (1990). "Acceleration of growth in two children treated with human growth hormone-releasing factor." New England Journal of Medicine, 312(1), 4-9.

2. Vittone, J., et al. (1997). "Effects of single nightly injections of growth hormone-releasing hormone (GHRH 1-29) in healthy elderly men." Metabolism, 46(1), 89-96.

3. Walker, R.F. (2006). "Sermorelin: a better approach to management of adult-onset growth hormone insufficiency?" Clinical Interventions in Aging, 1(4), 307-314.

4. Merriam, G.R., et al. (1997). "Growth hormone-releasing hormone (GHRH) treatment of age-related elevations of body fat." Endocrine, 7(1), 29-33.

5. Corpas, E., et al. (1992). "Human growth hormone and human aging." Endocrine Reviews, 14(1), 20-39.

Summary

Sermorelin stands as one of the most established GHRH analogs with a history of FDA approval and clinical use. Its ability to stimulate natural growth hormone production while preserving physiological feedback mechanisms makes it a valuable compound for both clinical and research applications.

Key Points:

• Classification: GHRH analog (GRF 1-29)
• Mechanism: GHRH receptor activation, stimulates natural GH release
• FDA History: Was approved for diagnostic and therapeutic use
• Advantages: Preserves pulsatile release, natural feedback mechanisms
• Common Use: Often combined with GHRPs for synergistic effect
• Half-life: 10-20 minutes (short, requires multiple daily dosing)

The combination of historical clinical data, physiological mechanism, and compatibility with other peptides continues to make sermorelin a foundational compound in growth hormone research.