Sermorelin

What sermorelin is

Sermorelin is the synthetic 29-residue peptide corresponding to the N-terminal fragment of human growth hormone-releasing hormone (GHRH), with a C-terminal amide. Its sequence is identical to residues 1 to 29 of the native 44-residue hormone, and the literature refers to it variously as GRF(1-29)-NH2, GHRH(1-29)-NH2, hGRF(1-29) and, during the years it was a licensed medicine, by the brand name Geref.

The hypothalamic factor that drives pituitary growth hormone release had been postulated for decades but defied isolation, because the hypothalamus contains too little of it. The breakthrough came from pancreatic tumours in two patients with acromegaly that were secreting the factor in quantity. In 1982 Roger Guillemin's group at the Salk Institute reported the isolation, sequence and synthesis of a 44-residue peptide from one such tumour [1], and in the same year Jean Rivier, Wylie Vale and colleagues characterised a 40-residue form from the second patient's tumour [2]. Two years later Ling and colleagues isolated the hypothalamic peptide itself and confirmed that the tumour-derived sequences matched the native hormone [3].

The point that makes sermorelin a compound in its own right was already in the 1982 Nature paper: among the synthetic fragments Rivier and colleagues tested, the 29-residue amidated form retained full intrinsic activity and potency in vitro [2]. Residues 30 to 44 contribute nothing to receptor activation that a pituitary cell assay can measure, and a 29-mer is considerably cheaper to make than a 44-mer. That observation defined the minimal active fragment and the molecule later developed as a diagnostic agent and a paediatric medicine.

Structurally, sermorelin contains no cysteine, no non-natural residues and no lipid chain. It does contain a methionine at position 27, which is susceptible to oxidation, an asparagine at position 8 that is prone to deamidation, and an N-terminal Tyr-Ala dipeptide that is the substrate for the enzyme responsible for its short life in plasma. The peptide carries a net positive charge at neutral pH. The reference identifiers for the free peptide are in the table.

How the literature describes its mechanism

Unlike many compounds in a research catalogue, sermorelin has a defined receptor and a mechanism that is not in dispute. It is an agonist of the GHRH receptor, a class B (secretin-family) G-protein-coupled receptor expressed on the somatotroph cells of the anterior pituitary. Kelly Mayo cloned the rat receptor in 1992 and showed that it was pituitary-specific and coupled to adenylyl cyclase [4]. Agonist binding raises intracellular cyclic AMP, activates protein kinase A and drives both the release of stored growth hormone and transcription of the growth hormone gene. Because the receptor is expressed almost exclusively on somatotrophs, the pharmacology is narrow.

The structural basis of that interaction is now known at near-atomic resolution. Zhou and colleagues published a cryo-electron microscopy structure of the human GHRH receptor in complex with GHRH and the stimulatory G protein in 2020 [5]. It shows the characteristic class B arrangement in which the C-terminal half of the peptide, folded as an α-helix, binds the extracellular domain of the receptor, while the N-terminal residues insert into the transmembrane bundle and trigger activation. This is consistent with the 1982 observation: the N-terminus is the activating end, and the residues beyond 29 lie outside the core binding interface.

Two features of the native system shape how sermorelin behaves in any biological preparation. The first is that GHRH does not act alone: growth hormone release reflects the interplay of GHRH, which stimulates, somatostatin, which inhibits, and ghrelin acting at a separate receptor (GHS-R1a) that synergises with GHRH, so the response to a GHRH-receptor agonist depends on the somatostatin tone of the preparation. The second is negative feedback: growth hormone and insulin-like growth factor I (IGF-I) both suppress GHRH release and increase somatostatin release, so a GHRH analogue cannot drive the axis indefinitely. This is often called a "physiological" property, but it is a statement about the intact axis, not about the compound.

The limiting factor in the pharmacology of the native hormone and of sermorelin is enzymatic. Frohman and colleagues showed in 1989 that human GHRH incubated in plasma is cleaved very rapidly between Ala2 and Asp3 by dipeptidyl peptidase IV (DPP-IV), yielding GHRH(3-44), which is essentially inactive at the receptor; a slower trypsin-like cleavage follows [6]. Because sermorelin retains the native Tyr-Ala N-terminus, it is subject to exactly the same cleavage. The consequence is a plasma half-life measured in minutes rather than hours, and every subsequent GHRH analogue of note has been designed around this fact, as discussed under related compounds.

For in-vitro work the relevant readouts are cyclic AMP accumulation and growth hormone release from primary pituitary cells or somatotroph lines, and binding or functional assays in cells expressing the GHRH receptor. The compound is active at nanomolar and sub-nanomolar concentrations in such systems, and is more often the reference agonist against which modified analogues are compared than the object of study itself.

The research record

Sermorelin is unusual among the compounds in this catalogue in having a full regulatory development history, including controlled trials in the population for which it was licensed. That history is evidence about a medicine that no longer exists; it neither validates nor describes the research material sold here.

Diagnostic use. The first licensed application was as a provocation agent: a bolus of GHRH(1-29) stimulates growth hormone release from a functioning pituitary, and a blunted response can help distinguish pituitary from hypothalamic causes of deficiency. Geref was approved in the United States for this purpose on 28 December 1990 (NDA 19-863) [12]. The test was never regarded as decisive, because the response in normal subjects is itself variable.

Paediatric growth hormone deficiency. The therapeutic licence followed in 1997 (NDA 20-443), for idiopathic growth hormone deficiency in children with growth failure [12]. The pivotal study was reported by Thorner and the Geref International Study Group in 1996: a multicentre trial in prepubertal children given GHRH(1-29)-NH2 once daily for a year, in which growth velocity roughly doubled from baseline and most children responded [7]. The rationale was that most idiopathic growth hormone deficiency is hypothalamic rather than pituitary in origin, so the pituitary can respond if given the signal. The 1999 review by Prakash and Goa is the most complete single account of the compound as a medicine [8]. Its conclusion was measured: sermorelin accelerated growth and was well tolerated, with injection-site reactions and occasional antibody formation the main findings, but the growth response was less than with recombinant growth hormone, and the requirement for a responsive pituitary limited the population in which it could be used.

Older adults. The second body of clinical work came from the Gerontology Research Center of the US National Institute on Aging, led by Marc Blackman, and it is the origin of nearly everything since said about sermorelin and ageing. Corpas and colleagues reported in 1992 that two weeks of GHRH(1-29) in a small group of healthy men in their seventies raised growth hormone and IGF-I concentrations into the range typical of young adults [9]. Vittone and colleagues followed in 1997 with a six-week study in healthy men aged 64 to 76, and found increased growth hormone and IGF-I, modest changes in some measures of strength and skin thickness, and little change in body composition [10]. These were small, short studies in healthy volunteers, measuring biochemical surrogates rather than clinical outcomes. They established that the aged pituitary still responds to a GHRH analogue. They did not establish any benefit, and their authors did not claim one.

Withdrawal of the licence. EMD Serono, the US affiliate of Merck KGaA, held both NDAs. In July 2008 it notified the FDA that the diagnostic ampoule was being discontinued; in December 2008 it discontinued the therapeutic vial and asked for both approvals to be withdrawn, which the FDA did with effect from June 2009. The company's statement gave the reason as the active ingredient no longer being manufactured, and the FDA later determined formally, in a 2013 Federal Register notice, that neither product had been withdrawn for reasons of safety or effectiveness [12]. The compound has not been marketed as a licensed medicine anywhere since, and was never authorised in the United Kingdom or by the European Medicines Agency.

The compounded "anti-ageing" product. The 2013 determination has had a consequence its authors probably did not intend. Because Geref was found to have been withdrawn for commercial rather than safety reasons, compounding pharmacies in the United States have treated the finding as support for preparing sermorelin acetate on prescription. A 2006 commentary by Richard Walker, arguing that sermorelin was a "better approach" to adult-onset growth hormone insufficiency than recombinant growth hormone, is frequently cited in that marketing [11]; it is a two-page opinion piece, not a trial, and the data it draws on are the NIA studies above. Sermorelin has since become one of the most heavily promoted compounded peptides in the US, sold through telehealth and "longevity" clinics with claims about sleep, body composition, recovery and ageing that go well beyond anything the literature supports. No controlled trial of sermorelin for any of those outcomes in adults has been published.

That product is not what is sold here. A compounded preparation is a pharmaceutical dosage form, prepared for a named patient under pharmacy supervision, usually as sermorelin acetate in a preserved multi-dose vial. The research material on this page is a lyophilised reference peptide for laboratory use, characterised by chromatography and mass spectrometry, supplied without preservative or excipient, and neither intended nor suitable for administration to anybody. The two share a sequence and nothing else.

Taking the record as a whole. Sermorelin is a well-characterised GHRH-receptor agonist with a known structure, a short enzymatic half-life, a withdrawn paediatric licence supported by controlled trials, and a small set of short studies in healthy older adults from a single group. It is a sound reference agonist for in-vitro work on the GHRH receptor. It is not a basis for therapeutic or anti-ageing claims of any kind, and this page makes none.

Regulatory status in the United Kingdom

Sermorelin is not licensed as a medicine in the United Kingdom. It has never held a UK marketing authorisation, is not in the British Pharmacopoeia, and the former US product Geref was withdrawn in 2008–2009 and has not been replaced [12]. BuyUK Peptides supplies sermorelin as a research chemical for in-vitro laboratory use under the Terms of Sale. It is not for human or veterinary administration. Purchasers must be 18 or over and are responsible for ensuring their use of the material complies with the laws and institutional rules that apply to them. Our guide to the UK rules on research compounds sets this out in more detail.

The World Anti-Doping Agency's Prohibited List names sermorelin explicitly. Section S2.2.4 of the 2026 List, in force from 1 January 2026, prohibits "growth hormone-releasing hormone (GHRH) and its analogues (e.g. CJC-1293, CJC-1295, sermorelin and tesamorelin)" under growth hormone releasing factors, within category S2 (peptide hormones, growth factors, related substances and mimetics) [16]. Category S2 applies at all times, in and out of competition. UK Anti-Doping applies the WADA List in full, and any researcher whose institution is subject to anti-doping rules should be aware of this.

Handling, storage and stability

Sermorelin is supplied lyophilised in a glass vial with a rubber stopper and an aluminium flip-off crimp. It is a mid-length, unlipidated, cysteine-free peptide and is straightforward to handle, with two chemical liabilities that deserve attention: oxidation of Met27 and deamidation of Asn8. Neither is rapid in the dry state at low temperature, but both proceed in solution, and oxidation is accelerated by light, dissolved oxygen and trace metals.

Sealed vial. Store at 2–8 °C for routine use and at −20 °C or below for storage beyond a few months. Protect from light. Avoid repeated freeze–thaw cycles. Allow a refrigerated vial to reach room temperature before opening, so that moisture does not condense onto the cake.

Reconstitution. For most in-vitro work the compound is reconstituted in sterile bacteriostatic water, sterile water, or a buffer appropriate to the assay. A basic 29-mer of this kind dissolves readily in water and in buffers at neutral or mildly acidic pH; add the solvent down the side of the vial and swirl gently rather than vortexing. The reconstitution calculator gives the volume to add for a target concentration. Working dilutions for cell assays are usually made into medium containing a little albumin immediately before use, since a cationic peptide at low concentration adsorbs to untreated plastic.

Reconstituted solution. Keep at 2–8 °C and protect from light. The half-life data in the literature concern enzymatic cleavage in plasma [6] and say nothing about the chemical stability of a clean aqueous solution; but methionine oxidation and asparagine deamidation do occur in solution, and the conservative practice is to use a research solution within 28 days, or to aliquot into single-use volumes and freeze at −20 °C. A solution stored for some time should be checked by HPLC before use in a quantitative assay. Discard any solution that becomes cloudy.

DPP-IV in biological media. Serum and some cell preparations contain DPP-IV activity. Where sermorelin sits in serum-containing medium or with cells that express the enzyme for more than a few minutes, it will be converted to the inactive (3-29) fragment and the apparent potency will fall. This is the commonest reason for inconsistent results with native-sequence GHRH analogues; a DPP-IV inhibitor or a serum-free protocol is the usual remedy.

Solubility. Sermorelin acetate is freely soluble in water and in common aqueous buffers at research concentrations. Where filtration is required a 0.22 µm low-binding (PVDF or PES) membrane is preferable to nylon for a cationic peptide.

What a sound certificate for sermorelin looks like

Every batch we release carries an independent certificate of analysis, and the figures from it are transcribed on the product page and in the certificate register. For sermorelin a certificate should contain the following, and a reader should be able to check each item against this monograph.

Purity by RP-HPLC. Reversed-phase HPLC on a C18 column with UV detection at 214 or 220 nm reports purity as the area of the main peak as a percentage of all integrated peaks. A good batch of sermorelin shows a single dominant peak with purity of 98% or above. The impurities of concern in a 29-mer are deletion sequences, the Met27 sulphoxide, which elutes slightly earlier than the parent, and the Asn8-deamidated species, which elutes slightly later; a certificate that shows the chromatogram is therefore more informative than one that reports a number alone.

Identity by LC-MS. Electrospray mass spectrometry confirms that the main peak has the expected mass. For sermorelin the average molecular weight is 3357.9 Da and the monoisotopic mass is 3355.82 Da. A peptide of this size and charge rarely appears as the singly charged ion; the characteristic signals are [M+3H]3+ at about 1120.3, [M+4H]4+ at about 840.5 and [M+5H]5+ at about 672.6, and a certificate may report any of these or a deconvoluted mass. The observed mass should agree with the theoretical value to within about 0.5 Da. A mass 16 Da higher than expected indicates methionine oxidation.

Net peptide content. Lyophilised peptides contain bound water and counter-ions, usually trifluoroacetate from purification or acetate after an exchange step, so the mass of powder in the vial is more than the mass of peptide. For a basic peptide with six cationic residues the counter-ion fraction is substantial, and net peptide content for sermorelin is typically 80–90%. Where reported, it matters for preparing solutions of accurate concentration.

Endotoxin. Where the batch has been tested, a limulus amoebocyte lysate (LAL) result is reported in endotoxin units per milligram. This is relevant to the primary pituitary cell cultures in which GHRH analogues are most often assayed, where endotoxin can alter hormone secretion on its own.

Our guide to reading a certificate of analysis goes through a complete report line by line.

Related compounds

Every other GHRH analogue in the catalogue is best understood as an attempt to solve the problem Frohman described in 1989 [6]: that the native N-terminus is cut by DPP-IV within minutes.

Tesamorelin takes the full 44-residue sequence and adds a trans-3-hexenoyl group to the N-terminal tyrosine, which hinders DPP-IV cleavage. It is the one GHRH analogue currently licensed anywhere, approved in the United States in 2010 for HIV-associated abdominal fat accumulation on the basis of the trials reported by Falutz and colleagues [15]. Mechanistically it is the same agonist at the same receptor; the difference is duration.

Mod GRF 1-29, also sold as "CJC-1295 without DAC", is sermorelin with four substitutions: D-Ala2, which blocks DPP-IV; Gln8, which removes the deamidation site; Ala15, which stabilises the helix; and Leu27, which removes the oxidisable methionine. Jetté and colleagues described those changes in 2005 as the peptide core of CJC-1295, to which a maleimidopropionic acid linker (the "drug affinity complex") was attached so that the analogue would bind covalently to serum albumin and circulate for days [13]; Teichman and colleagues showed in 2006 that the conjugate raised growth hormone and IGF-I in healthy adults for a week or more after a single administration [14]. Mod GRF 1-29 is the tetrasubstituted peptide without the linker; it resists DPP-IV but is otherwise cleared as rapidly as sermorelin. Any study of a modified analogue needs the native-sequence fragment alongside it to show what the modifications have changed.

Ipamorelin is not a GHRH analogue but a growth hormone secretagogue acting at the ghrelin receptor, GHS-R1a. The two receptors synergise, and GHRH analogues and GHS-R agonists are often studied together in pituitary cell preparations to characterise that interaction.

Frequently asked questions

Is sermorelin the same as GHRH? It is the first 29 of the 44 residues of human GHRH, with a C-terminal amide. The 1982 characterisation showed that this fragment has full potency at the receptor in vitro [2].

Was it ever a licensed medicine? Yes. Geref was approved in the United States as a diagnostic agent in 1990 and for paediatric growth hormone deficiency in 1997; both approvals were withdrawn at the company's request in 2008–2009 for commercial reasons, not safety [12]. It was never licensed in the United Kingdom, and the research material sold here is not Geref.

Why does it have such a short half-life? DPP-IV in plasma cleaves the N-terminal Tyr-Ala almost immediately, leaving an inactive fragment [6]. Mod GRF 1-29 and tesamorelin modify or protect the N-terminus to prevent this.

Is it on the WADA list? Yes, by name, under S2.2.4 (growth hormone releasing factors), at all times [16].

Can this material be used in humans? No. It is supplied for in-vitro research only.

How long does a sealed vial last? Lyophilised peptides of this kind are stable for years at −20 °C and for many months at 2–8 °C. The batch certificate reports the test date; the storage guidance on this page applies from receipt.

References

1. Guillemin R, Brazeau P, Böhlen P, Esch F, Ling N, Wehrenberg WB. Growth hormone-releasing factor from a human pancreatic tumor that caused acromegaly. Science. 1982;218(4572):585–587. doi:10.1126/science.6812220.
2. Rivier J, Spiess J, Thorner M, Vale W. Characterization of a growth hormone-releasing factor from a human pancreatic islet tumour. Nature. 1982;300(5889):276–278. doi:10.1038/300276a0.
3. Ling N, Esch F, Böhlen P, Brazeau P, Wehrenberg WB, Guillemin R. Isolation, primary structure, and synthesis of human hypothalamic somatocrinin: growth hormone-releasing factor. Proceedings of the National Academy of Sciences. 1984;81(14):4302–4306. doi:10.1073/pnas.81.14.4302.
4. Mayo KE. Molecular cloning and expression of a pituitary-specific receptor for growth hormone-releasing hormone. Molecular Endocrinology. 1992;6(10):1734–1744. doi:10.1210/mend.6.10.1333056.
5. Zhou F, Zhang H, Cong Z, et al. Structural basis for activation of the growth hormone-releasing hormone receptor. Nature Communications. 2020;11:5205. doi:10.1038/s41467-020-18945-0.
6. Frohman LA, Downs TR, Heimer EP, Felix AM. Dipeptidylpeptidase IV and trypsin-like enzymatic degradation of human growth hormone-releasing hormone in plasma. Journal of Clinical Investigation. 1989;83(5):1533–1540. doi:10.1172/JCI114049.
7. Thorner M, Rochiccioli P, Colle M, et al. Once daily subcutaneous growth hormone-releasing hormone therapy accelerates growth in growth hormone-deficient children during the first year of therapy. Geref International Study Group. Journal of Clinical Endocrinology and Metabolism. 1996;81(3):1189–1196. doi:10.1210/jcem.81.3.8772599.
8. 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):139–157. doi:10.2165/00063030-199912020-00007.
9. Corpas E, Harman SM, Piñeyro MA, Roberson R, Blackman MR. Growth hormone (GH)-releasing hormone-(1-29) twice daily reverses the decreased GH and insulin-like growth factor-I levels in old men. Journal of Clinical Endocrinology and Metabolism. 1992;75(2):530–535. doi:10.1210/jcem.75.2.1379256.
10. Vittone J, Blackman MR, Busby-Whitehead J, et al. Effects of single nightly injections of growth hormone-releasing hormone (GHRH 1-29) in healthy elderly men. Metabolism. 1997;46(1):89–96. doi:10.1016/S0026-0495(97)90174-8.
11. Walker RF. Sermorelin: a better approach to management of adult-onset growth hormone insufficiency? Clinical Interventions in Aging. 2006;1(4):307–308. doi:10.2147/ciia.2006.1.4.307.
12. US Food and Drug Administration. Determination that GEREF (sermorelin acetate) injection, 0.5 milligrams base/vial and 1.0 milligrams base/vial, and GEREF (sermorelin acetate) injection, 0.05 milligrams base/amp, were not withdrawn from sale for reasons of safety or effectiveness. Federal Register. 2013;78(42):14095–14096. Docket FDA-2012-P-1071. govinfo.gov.
13. Jetté L, Léger R, Thibaudeau K, et al. Human growth hormone-releasing factor (hGRF)1–29-albumin bioconjugates activate the GRF receptor on the anterior pituitary in rats: identification of CJC-1295 as a long-lasting GRF analog. Endocrinology. 2005;146(7):3052–3058. doi:10.1210/en.2004-1286.
14. Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA. Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults. Journal of Clinical Endocrinology and Metabolism. 2006;91(3):799–805. doi:10.1210/jc.2005-1536.
15. Falutz J, Allas S, Blot K, et al. Metabolic effects of a growth hormone-releasing factor in patients with HIV. New England Journal of Medicine. 2007;357(23):2359–2370. doi:10.1056/NEJMoa072375.
16. World Anti-Doping Agency. The Prohibited List 2026. Effective 1 January 2026. Section S2.2.4, growth hormone releasing factors. wada-ama.org/en/prohibited-list.

This monograph summarises the published literature for laboratory researchers. It is not medical advice, and nothing on this site is for human or veterinary use.