Sermorelin is the first 29 amino acids of growth hormone-releasing hormone, with an amidated C-terminus. The full hormone is 44 residues; truncation work established that everything after position 29 is dispensable for receptor activity, and sermorelin is what remains.
That makes it the reference molecule for an entire family. CJC-1295 and tesamorelin are both GHRH(1-29) with modifications added; understanding what sermorelin is and why it disappears so quickly explains what those modifications are for. This post covers the truncation, the amide, the degradation route, and what the certificate reports.
Where the sequence came from
Growth hormone-releasing hormone was isolated in 1982 by Guillemin and colleagues — from a pancreatic tumour, not from hypothalamus, which is an accident of the biology: the tumour produced it in quantities large enough to purify, and it had caused acromegaly in the patient. That is how the sequence was obtained.
The native hormone is 44 residues. Systematic truncation showed that activity at the GHRH receptor survives removal of residues 30–44 and collapses when the N-terminus is disturbed. The receptor-binding information is concentrated at the front of the molecule.
So GHRH(1-29) retains the activity and loses half the synthesis. That is the entire rationale for sermorelin, and the reason every later GHRH analogue starts from the same 29-residue scaffold.
The C-terminal amide is not optional
Sermorelin is GHRH(1-29) amide — the C-terminal carboxyl group is replaced by an amide (–CONH₂).
This matters for two reasons.
Activity. Truncating a peptide leaves an artificial C-terminus carrying a negative charge the native sequence did not have at that position. Amidation neutralises it and better mimics the continuing chain.
Identity. An amide weighs approximately one dalton less than the corresponding free acid. On a certificate, that single dalton is the difference between the right molecule and a different one. How a peptide sequence is verified covers why mass spectrometry resolves differences at this scale and why purity cannot.
Why the half-life is minutes
Sermorelin is cleared fast, and the dominant route is enzymatic.
Frohman and colleagues showed in 1986 that GHRH is cleaved in plasma between residues 2 and 3 — Ala² and Asp³ — by dipeptidyl peptidase-4, producing GHRH(3-44), which is biologically inactive. The same cleavage applies to the truncated analogue. Removing the first two residues destroys the receptor-binding N-terminus the truncation studies showed was essential.
This is the same enzyme and the same vulnerability that native GLP-1 has, and it is why semaglutide and tirzepatide both carry Aib substitutions near their N-termini. Sermorelin has no such protection. It is the unmodified molecule.
Renal clearance removes what the enzyme does not. At 3357 Da, sermorelin is well below the glomerular filtration threshold and carries no albumin-binding group to keep it in circulation — the strategy described in why acylated peptides last a week.
What the family did about it
| Compound | What it is | Change from sermorelin |
|---|---|---|
| Sermorelin | GHRH(1-29) amide | — the parent |
| CJC-1295 without DAC | GHRH(1-29) with four substitutions | Aib and other residue swaps resisting enzymatic cleavage |
| CJC-1295 with DAC | The above plus a maleimide linker | Binds serum albumin covalently; half-life measured in days |
| Tesamorelin | GHRH(1-44) with an N-terminal trans-3-hexenoyl group | Acylation blocks N-terminal attack; full-length rather than truncated |
Every entry in that table is an answer to the same problem — the two-minute enzymatic cleavage at the N-terminus — approached differently. CJC-1295 with DAC vs without DAC covers the DAC distinction, CJC-1295 without DAC and modified GRF 1-29 covers the substitutions, and ipamorelin vs CJC-1295 vs tesamorelin compares the family.
Ipamorelin belongs to a different class entirely — a ghrelin receptor agonist, not a GHRH analogue — and is frequently blended with CJC-1295 for that reason.
What the certificate reports
| Field | Lot SERMO5-0318 |
|---|---|
| Molecular weight | 3357.5 |
| Purity (RP-HPLC, 214 nm) | 99.8% |
| Identity | MALDI-MS |
| Endotoxin | ≤0.05 EU/mL |
| Label | 5 mg |
Note the identity method is MALDI-MS rather than LC-MS/MS here. Both are mass spectrometry and both confirm molecular weight; they differ in ionisation and in whether chromatographic separation precedes the measurement. What LC-MS confirms covers the distinction and why either is adequate for identity.
The endotoxin line uses ≤ rather than < on this lot — a reporting convention difference between runs, not a different result. What "non-pyrogenic" means covers what the figure represents.
Handling
Unmodified, unacylated, moderately sized and water-soluble. Sermorelin is straightforward compared with the acylated analogues.
| Property | Behaviour |
|---|---|
| Dissolution | Readily soluble; no hydrophobic chain to resist wetting |
| Stability in solution | Poorer than the modified analogues — the same bonds enzymes attack are chemically ordinary |
| Adsorption | Real at low concentration — why peptides stick to plastic |
| Freeze-thaw | Aliquot rather than cycle — aliquoting and freeze-thaw cycles |
| Storage | Standard lyophilized handling — how to store peptide vials |
There is one residue worth noting: Met²⁷ is an oxidation site. Methionine oxidises readily in solution, adding 16 Da and potentially altering activity. Oxidation-prone residues in peptides covers the mechanism; in practice it argues for cold, dark, short-duration storage of reconstituted material.
Regulatory position
Sermorelin was an approved prescription medicine in the United States — marketed as Geref for paediatric growth hormone deficiency diagnosis and treatment — and was discontinued commercially, not withdrawn for safety. Prakash and Goa's 1999 review covers that clinical record.
A discontinued approval is not a current one. Research-grade sermorelin is not an approved product, is not interchangeable with one, and is supplied here for laboratory research only. What "research use only" means covers what that designation does.
Frequently asked questions
Why 29 residues and not the full 44?
Truncation studies showed residues 30–44 are not required for receptor activity. GHRH(1-29) is the shortest fragment retaining it, so it is the efficient synthesis target.
What does the amide at the end do?
It neutralises the artificial negative charge created by truncating the chain, better mimicking the native sequence. It also changes the molecular weight by about one dalton, which is how a certificate distinguishes it from the free acid.
Why is sermorelin's half-life so much shorter than CJC-1295's?
Because it has no protection against DPP-4 cleavage at the N-terminus and no albumin-binding group. CJC-1295 adds both. Sermorelin is the unmodified parent molecule.
Is sermorelin the same as GRF(1-29)?
Yes. Growth hormone-releasing factor and growth hormone-releasing hormone are two names for the same hormone, and 1-29 is the same fragment. Why one peptide has five names covers how this happens.
Does the certificate show the amide form specifically?
The molecular weight does. 3357.5 Da corresponds to the amide; the free acid would be approximately one dalton heavier. That is the only place on the certificate where the distinction appears.
Why was Geref discontinued if it was approved?
Commercial reasons rather than safety. A discontinued product is not evidence of a problem, but it also means there is no current approved sermorelin product to reference.
References
- Guillemin R, Brazeau P, Bohlen P, et al. Growth hormone-releasing factor from a human pancreatic tumor that caused acromegaly. Science 1982;218(4572):585-7. doi.org/10.1126/science.6812220
- Prakash A, Goa KL. Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency. BioDrugs 1999;12(2):139-57. doi.org/10.2165/00063030-199912020-00007
- Frohman LA, Downs TR, Williams TC, et al. Rapid enzymatic degradation of growth hormone-releasing hormone by plasma in vitro and in vivo to a biologically inactive product cleaved at the NH2 terminus. Journal of Clinical Investigation 1986;78(4):906-13. doi.org/10.1172/JCI112679
Every product mentioned is sold for laboratory research use only and is not for human or animal use. Nothing on this page describes or recommends use of the material sold here in humans or animals.
