Sermorelin
Sermorelin is a synthetic peptide consisting of the first 29 amino acids of human growth hormone releasing hormone (GHRH). It was previously FDA-approved as Geref but has been discontinued in the US.
Overview
Sermorelin is the 29-residue N-terminal fragment of human growth hormone releasing hormone, the hypothalamic peptide that stimulates growth hormone release from the pituitary. Research in the 1980s showed that this fragment retains the biological activity of the full 44-residue hormone, making it a practical synthetic target. Sermorelin acetate was developed as a drug and marketed in the US under the brand name Geref.
Geref was studied in children with growth hormone deficiency and was also used as a diagnostic agent for assessing pituitary growth hormone reserve. It has since been discontinued in the US. Sermorelin remains a reference compound in GHRH research and is the parent sequence from which several later analogues, including CJC-1295 and modified GRF(1-29), were derived. Its short duration of action is its main pharmacological limitation.
Compare: Sermorelin vs Tesamorelin, CJC-1295 vs sermorelin.
Structure
Sermorelin corresponds to residues 1–29 of human GHRH, with an amidated C-terminus. The sequence is natural and unmodified apart from the amide, which means it is susceptible to rapid cleavage by dipeptidyl peptidase-4 between positions 2 and 3, as well as to methionine oxidation and asparagine deamidation. It has historically been formulated as the acetate salt. Stabilized analogues of this sequence were later developed by introducing substitutions at positions such as 2, 8, 15 and 27.
Mechanism
Sermorelin binds the GHRH receptor, a class B G protein-coupled receptor on somatotroph cells of the anterior pituitary. Receptor activation raises cyclic AMP and stimulates both synthesis and release of growth hormone. Growth hormone then drives hepatic production of IGF-1, which feeds back to suppress further release.
Because sermorelin acts upstream of growth hormone, its effect depends on a functioning pituitary and remains subject to inhibition by somatostatin. This is the basis for its historical diagnostic use: a growth hormone response to sermorelin indicates that the pituitary can secrete growth hormone. Its short half-life means it produces brief pulses of release rather than sustained elevation.
Research
Pediatric growth hormone deficiency
Sermorelin was evaluated in clinical trials in children with idiopathic growth hormone deficiency, which supported the original approval of Geref. These studies compared growth responses with those expected from recombinant growth hormone therapy. Recombinant growth hormone became the dominant option in this area, and sermorelin is no longer marketed in the US. The historical trial data are the main body of human efficacy evidence for the compound.
Diagnostic testing of pituitary reserve
Sermorelin was used to test whether the pituitary could release growth hormone in response to GHRH stimulation. Such testing helped distinguish hypothalamic from pituitary causes of deficiency, because a pituitary that responds to sermorelin implies the defect lies upstream. Other stimulation tests are used in current endocrine practice, and the diagnostic role of sermorelin is now mainly of historical interest.
Aging and the somatotropic axis
Growth hormone secretion declines with age, and small clinical studies in older adults examined whether GHRH(1-29) could restore more youthful growth hormone and IGF-1 patterns. These studies were limited in size and duration, and they did not establish clinical benefit. They are mainly cited as physiological research into the responsiveness of the aging pituitary rather than as evidence for any intervention. Interpretation is limited by small sample sizes.
Regulatory status
Sermorelin was previously approved by the FDA as Geref (sermorelin acetate) but has been discontinued in the US, so there is no currently marketed FDA-approved sermorelin product. Its status for pharmacy compounding should be checked against current FDA guidance. GHRH and its analogues are prohibited at all times under section S2 of the WADA Prohibited List.
Status changes often. See the regulatory tracker for dated updates.
Quality and identity testing
A COA should confirm identity by mass spectrometry, with the observed mass matching the expected mass for GHRH(1-29) amide shown on this page, and report purity by reverse-phase HPLC. As a natural 29-residue sequence, sermorelin is prone to methionine oxidation (+16 Da), asparagine deamidation (+1 Da), and the des-Tyr-Ala (3–29) fragment produced by dipeptidyl peptidase-type cleavage; a well-resolved HPLC method should separate these. Confirm the C-terminal amide rather than the free acid. Because modified GRF(1-29) has a similar length but a different mass, MS also guards against substitution. Counter-ion and net peptide content should be reported.
Open Sermorelin in the sequence analyzer to see the expected [M+H]+ and multiply charged ions for an MS identity check (set the N-acetyl, amide and disulfide options to match).
For a walkthrough of each section of a certificate, see how to read a COA.
Storage and stability
Store lyophilized sermorelin sealed at -20 °C, protected from light and moisture. The unmodified sequence is more labile than its stabilized analogues: methionine oxidation and asparagine deamidation proceed in solution, especially at higher pH and temperature. Reconstituted laboratory solutions should be refrigerated, used within a short period, aliquoted to avoid repeated freeze-thaw cycles, and protected from light. Use low-binding tubes, since GHRH peptides can adsorb to surfaces at low concentration.
Download the Sermorelin data sheet (PDF): sequence, masses, expected MS ions and handling on one printable page.
Latest research
The newest PubMed-indexed papers that mention Sermorelin in their title or abstract, retrieved through Europe PMC and refreshed automatically. Inclusion is not an endorsement of a paper's findings.
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Frequently asked questions
Is sermorelin FDA approved?
Sermorelin was previously FDA-approved under the brand name Geref, but that product has been discontinued in the US. There is currently no marketed FDA-approved sermorelin product. Its status in pharmacy compounding should be checked against current FDA guidance rather than assumed. Historical clinical data from the Geref program remain the main human evidence base.
What is the difference between sermorelin and tesamorelin?
Sermorelin is the first 29 residues of human GHRH and is degraded quickly. Tesamorelin is the full 44-residue GHRH sequence with a trans-3-hexenoyl group on the N-terminus, which improves stability. Tesamorelin is FDA-approved as Egrifta for a specific indication, while sermorelin's approved product has been discontinued. Both act on the same GHRH receptor in the pituitary.
Is sermorelin the same as growth hormone?
No. Sermorelin is a fragment of growth hormone releasing hormone, a hypothalamic signal that tells the pituitary to release growth hormone. Growth hormone itself is a much larger protein of 191 amino acids made by the pituitary. Sermorelin acts upstream and depends on a functioning pituitary gland. It is also chemically synthesized, whereas growth hormone is produced recombinantly.
Related compounds
- Tesamorelin
Tesamorelin is a stabilized synthetic analogue of human growth hormone releasing hormone. It is FDA-approved as Egrifta for reducing excess abdominal fat in adults with HIV-associated lipodystrophy.
- CJC-1295
CJC-1295 is a synthetic analogue of growth hormone releasing hormone (GHRH). The name properly refers to a version with a drug affinity complex (DAC) that binds albumin, but is also applied to modified GRF(1-29), which lacks DAC.
- Ipamorelin
Ipamorelin is a synthetic pentapeptide growth hormone secretagogue that acts as a selective agonist of the ghrelin receptor (GHS-R1a). It is investigational and not approved for any use.
- IGF-1 LR3
IGF-1 LR3 is a recombinant analogue of insulin-like growth factor 1 with an arginine substitution at position 3 and a 13-residue N-terminal extension. It binds IGF-binding proteins weakly and is widely used in cell culture.
References
- PubMed: all indexed literature on Sermorelin
- ClinicalTrials.gov: registered studies mentioning Sermorelin
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