Sermorelin: what it is, how it works and what studies have found

Sermorelin is the first 29 amino acids of human growth hormone-releasing hormone (GHRH), made synthetically and finished as a C-terminal amide. It is a growth hormone secretagogue: it does not contain growth hormone, but binds the GHRH receptor in the anterior pituitary and prompts somatotroph cells to release their own. It was approved in the United States as a diagnostic agent in 1990 and as a treatment for idiopathic growth hormone deficiency in children in 1997, and both products were discontinued in 2008 [1] [2] [3].

This overview covers the chemistry, the receptor pharmacology, the regulatory history (with dates from FDA’s own records), the published clinical studies, and how sermorelin compares with tesamorelin and CJC-1295. It is written for laboratory researchers and is not medical guidance.

What is sermorelin?

Human GHRH was isolated in 1982 from pancreatic tumours that had caused acromegaly. Two groups sequenced it: Guillemin’s laboratory reported a 44-residue amidated peptide, and Rivier, Spiess, Thorner and Vale characterised a growth hormone-releasing factor from a human pancreatic islet tumour in Nature [4] [5]. The mature hypothalamic hormone is residues 32–75 of the 108-residue precursor, with a leucine amide at its C-terminus [6].

Sermorelin is the N-terminal 29-residue portion of that 44-residue hormone, GHRH(1-29)-NH2, and its synonyms in PubChem include hGHRH(1-29)NH2 and GRF(1-29)NH2 [7]. The fragment is used because residues 1–29 carry the receptor-activating part of the molecule; a 1999 drug review describes it as a 29-amino-acid analogue of human GHRH that specifically stimulates growth hormone secretion from the anterior pituitary [8].

Sermorelin structure, sequence and molecular weight

Property	Sermorelin
INN	Sermorelin (marketed as sermorelin acetate)
CAS number	86168-78-7 [7]
Molecular formula	C149H246N44O42S [7]
Molecular weight	3357.9 g/mol (free peptide) [7]
Sequence (one-letter)	YADAIFTNSYRKVLGQLSARKLLQDIMSR-NH2 [7]
Sequence (three-letter)	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
Length	29 residues
Modifications	C-terminal amide only; native sequence, no non-natural residues, no lipid or PEG
Relationship to GHRH	Residues 1–29 of the 44-residue human hormone [4] [6]
Salt form	Acetate (FDA-approved products were sermorelin acetate) [3]
PubChem CID	16132413

Three features of the sequence matter in the laboratory. The single methionine at position 27 is the obvious oxidation site. Asn8 can deamidate. And the N-terminal Tyr-Ala dipeptide is the cleavage site for plasma dipeptidyl aminopeptidase, which is the main reason native GHRH peptides are short-lived (see the half-life section below). Later analogues target these positions: CJC-1295, for example, carries D-Ala2, Gln8 and Leu27 (plus Ala15) in place of the native residues [25].

Sermorelin mechanism of action

Sermorelin acts through the growth hormone-releasing hormone receptor (GHRHR, UniProt Q02643), a 423-residue G protein-coupled receptor. UniProt describes it as the receptor for GRF, coupled to G proteins that activate adenylyl cyclase, and as stimulating somatotroph cell growth, growth hormone gene transcription and growth hormone secretion [9]. When the receptor was cloned in 1992, cells expressing it bound human GHRH with high affinity and specificity and raised intracellular cAMP in response; the receptor belongs to the same family as the secretin and vasoactive intestinal peptide receptors, and in the rat its mRNA was expressed predominantly, if not exclusively, in the anterior pituitary [10].

The downstream effect is release of the pituitary’s own growth hormone, which then drives hepatic and peripheral IGF-1. Because the signal enters the axis at the pituitary rather than replacing growth hormone, output stays under the pituitary’s own control. A review of a related drug class, the growth hormone-releasing peptides and ibutamoren, makes the same argument for secretagogues generally: they promote pulsatile release that remains subject to negative feedback, which can prevent supra-therapeutic growth hormone levels [11]. Normal growth hormone responses to sermorelin do not exclude deficiency caused by a hypothalamic deficit, which is why the diagnostic use relied on pairing it with other provocative tests [8].

Sermorelin half-life and why GHRH(1-29) is short-lived

We did not find a peer-reviewed pharmacokinetic study that reports a plasma half-life for sermorelin itself, so we do not quote one. The best primary evidence concerns the parent hormone. In human plasma in vitro, intact GHRH(1-44)-NH2 disappeared with a half-life of 17 minutes by HPLC, converted to GHRH(3-44)-NH2, a fragment with less than one-thousandth of the parent’s biological activity. After intravenous administration in volunteers, the intact peptide’s half-life was 6.8 minutes, and the authors attributed the inactivation to a plasma dipeptidyl aminopeptidase [12].

Sermorelin carries the same Tyr1-Ala2 N-terminus, so the same enzyme can remove its first two residues. Doping-control chemists accordingly screen urine for both sermorelin and its primary metabolite [13]. This short exposure is the problem that every later GHRH analogue tries to solve: tesamorelin adds an N-terminal hexenoyl group to resist the enzyme, and CJC-1295 combines a D-alanine at position 2 with albumin binding.

Development history and FDA status timeline

Date	Event	Source
1982	Human GHRH isolated from pancreatic tumours and sequenced (44 residues, C-terminal amide)	[4] [5]
1987	Twice-daily subcutaneous GHRH(1-29)-NH2 tested in 18 prepubertal GH-deficient children	[14]
28 Dec 1990	FDA approves NDA 19-863, sermorelin acetate for evaluating the ability of the pituitary somatotroph to secrete growth hormone (new molecular entity)	[1] [3]
1996	Multicentre study of once-daily subcutaneous GHRH(1-29) in 110 GH-deficient children published	[15]
26 Sep 1997	FDA approves NDA 20-443, sermorelin acetate for idiopathic growth hormone deficiency in children with growth failure	[2] [3]
11 Jul and 2 Dec 2008	Holder (EMD Serono) notifies FDA that the diagnostic and treatment products are being discontinued	[3]
18 Jun 2009	FDA withdrawal of approval of NDA 19-863 and NDA 20-443 takes effect, at the holder’s request	[3]
4 Mar 2013	FDA determines the products were not withdrawn from sale for reasons of safety or effectiveness, which allows abbreviated applications that refer to them	[3]

The 2013 notice was triggered by a citizen petition. FDA reviewed its records and the published literature on postmarketing adverse events and concluded that neither product was withdrawn for safety or effectiveness reasons [3]. FDA’s notice does not state the commercial reason. A 2006 editorial described sermorelin as having been marketed for years for children with growth retardation but unable to compete with recombinant growth hormone, after which the manufacturer withdrew it [16]. Drugs@FDA still lists both applications as discontinued, flagged with the Federal Register determination [1] [2].

Key sermorelin studies and findings

Study	Design / phase	Population	n	Duration	Primary measure	Main finding	Ref
Ross et al. 1987	Open, uncontrolled	Prepubertal GH-deficient children	18	6–18 months	Height velocity	Height velocity rose in 12 of 18; 8 judged worthwhile responders (gain of more than 2 cm/yr)	[14]
Thorner et al. 1996	Open-label, multicentre	Previously untreated prepubertal GH-deficient children	110 (86 evaluable)	12 months	Height velocity	Mean height velocity 4.1 cm/yr at baseline, 8.0 at 6 months and 7.2 at 12 months; 74% good responders at 6 months	[15]
Prakash and Goa 1999	Review of clinical data	Children with idiopathic GHD	n/a	n/a	Diagnostic accuracy and growth	Intravenous sermorelin a rapid, relatively specific test of GH secretion; increases in height velocity sustained over 12 months	[8]
Vittone et al. 1997	Open, single-arm	Healthy men aged 64–76 with low IGF-I	11	6 weeks	Nocturnal GH, muscle function	Mean nocturnal GH release rose; IGF-I unchanged; 2 of 6 strength measures improved; body composition unchanged	[17]
Khorram et al. 1997 (analogue)	Single-blind, placebo run-in	Men and women aged 55–71	19	16 weeks active	GH, IGF-I, body composition	[Nle27]GHRH(1-29)-NH2 raised nocturnal GH and IGF-I; lean mass rose in men only; transient hyperlipidaemia	[18]

Growth hormone deficiency in children

The largest sermorelin efficacy dataset is the 1996 multicentre study. One hundred and ten previously untreated prepubertal children with growth hormone deficiency received once-daily subcutaneous GHRH(1-29) at bedtime for up to a year, and 86 were eligible for efficacy analysis. Mean height velocity rose from 4.1 ± 0.9 cm/yr at baseline to 8.0 ± 1.5 cm/yr at 6 months and 7.2 ± 1.3 cm/yr at 12 months, and 74% of the children were rated good responders at 6 months. The ratio of bone-age change to height-age change was not different from 1 at 12 months, and the investigators saw no change in fasting glucose and no excessive generation of IGF-I [15].

The study was open-label without a control arm, so the comparison is with each child’s own pre-treatment growth rate. The 1999 review noted that sermorelin had not been compared directly with somatropin at the recommended regimen, and that height-velocity gains in studies using other sermorelin regimens were smaller than with once-daily somatropin; its effect on final adult height had not been determined [8]. The earlier 1987 study had already shown that response was not universal: 12 of 18 children grew faster, and 8 were judged worthwhile responders [14].

Diagnostic use

The first approval was diagnostic. The review describes an intravenous sermorelin challenge as a rapid and relatively specific test for growth hormone deficiency, with fewer false-positive growth hormone responses in children without deficiency than other provocative tests, and notes adult data suggesting that sermorelin combined with arginine is more specific still [8].

Older adults

Interest in sermorelin outside paediatrics came from the age-related decline of the growth hormone and IGF-I axis. In 11 healthy men aged 64 to 76 years, six weeks of nightly subcutaneous GHRH(1-29) increased mean nocturnal growth hormone release, the area under the growth hormone peak and peak amplitude, without changing pulse frequency or IGF-I, IGFBP-3 or GH-binding protein. Two of six strength measures and one endurance test improved; weight, DEXA body composition, glucose, insulin and lipids did not change. The authors concluded that single nightly administration was less effective than multiple daily administration at producing GH- or IGF-I-mediated effects [17]. This was an uncontrolled study of 11 men, so the evidence is weak.

A related study used a close analogue, [Nle27]GHRH(1-29)-NH2, in which norleucine replaces methionine 27. In 19 adults aged 55 to 71, sixteen weeks of nightly administration after a four-week placebo period raised integrated nocturnal growth hormone and IGF-I, increased skin thickness in both sexes, and increased lean body mass and insulin sensitivity in men only. The only adverse effect reported was transient hyperlipidaemia [18]. Because the peptide differs from sermorelin at position 27, these results should not be read as sermorelin data.

Safety findings reported in studies

Across the paediatric programme, the 1999 review reported that single intravenous and repeated subcutaneous administration were well tolerated, with transient facial flushing and pain at the administration site the most common adverse events [8]. The 1996 study found no adverse changes in general biochemical or hormonal analyses [15], and the 1997 study in older men reported no significant adverse effects [17]. A review of growth hormone secretagogues (growth hormone-releasing peptides and ibutamoren) concluded that they are generally well tolerated but flagged possible rises in blood glucose through reduced insulin sensitivity, and called for long-term data on cancer incidence and mortality [11].

FDA’s 2013 review of postmarketing adverse-event literature found no safety reason for the withdrawal [3]. That is a statement about the approved paediatric and diagnostic uses; it does not establish safety for any other use.

Sermorelin regulatory status by region

Jurisdiction	Status	Ref
United States	Previously approved (1990 diagnostic; 1997 paediatric GHD). Both NDAs withdrawn effective 18 June 2009; listed as discontinued, not withdrawn for safety or effectiveness	[3] [2]
Sport (all WADA signatories)	Prohibited at all times under S2.2.4 (GHRH and its analogues, named example)	[19]
Other markets	We did not identify a currently marketed authorised sermorelin product in the EU, UK, India or China in the sources we reviewed; national rules on research-use peptides vary	n/a

Sermorelin in laboratory research

In current laboratory work, sermorelin and related GHRH(1-29) peptides appear mainly as reference GHRH agonists and analytical targets. Applications in the published literature include:

• Receptor pharmacology. Cells expressing the cloned human GHRH receptor respond to GHRH with cAMP production, which is the standard functional read-out for GHRH analogues [10].
• Pituitary cell secretion assays. Growth hormone release from cultured rat anterior pituitary cells was the bioassay used to rank GRF(1-29) analogues during the development of CJC-1295 [20].
• Stability and metabolism. HPLC tracking of the des-Tyr-Ala product in plasma is the classic way to measure dipeptidyl aminopeptidase cleavage of GHRH peptides [12].
• Anti-doping analytics. Validated nano-LC quadrupole/Orbitrap methods detect sermorelin and its primary metabolite in urine at or below 0.5 ng/mL [13]; the same method covers tesamorelin and CJC-1295 [13].

For identity and purity, the usual package is reversed-phase HPLC or UPLC for purity and related substances, LC-MS for intact mass (expected monoisotopic and average masses follow from C149H246N44O42S), and peptide mapping or MS/MS sequencing to confirm the order of residues. Counter-ion (acetate) and water content need to be measured to convert a gross weight into peptide content.

Synthesis, purity and impurities

Sermorelin is a 29-mer with no unusual residues, which makes it a routine target for Fmoc solid-phase peptide synthesis on an amide-forming resin, followed by preparative reversed-phase HPLC and lyophilization. The impurity classes to look for are the general ones for peptides of this length: deletion and truncated sequences from incomplete couplings, the Met27 sulfoxide from oxidation, Asn8 deamidation products, aspartimide-related variants at the two Asp residues, and incomplete C-terminal amidation (the free-acid form). Our guides to SPPS versus LPPS and peptide API impurities and specifications explain how these are controlled and how limits are set.

Purity matters more than usual for a GHRH agonist because the des-Tyr-Ala fragment is close to inactive [12]: a batch that has partially degraded can look acceptable by gross weight while carrying much less active peptide.

Storage and stability of lyophilized sermorelin

As a lyophilized acetate salt, sermorelin is stored like other research peptides: sealed, dry, protected from light, and frozen for long-term holding, with the container allowed to reach room temperature before opening to avoid condensation. Methionine oxidation and deamidation both accelerate with moisture, so residual water and headspace oxygen are the main levers. The general principles, including how cake moisture and temperature affect shelf life, are covered in our guide to lyophilised peptide stability and storage. This applies to laboratory material only.

Sermorelin vs tesamorelin

Tesamorelin is the full 44-residue GHRH sequence with a trans-3-hexenoyl group on Tyr1, a change that makes it resistant to dipeptidyl aminopeptidase-IV and slows its degradation in plasma [21]. It is an approved active ingredient in the US for excess abdominal fat in HIV-infected adults with lipodystrophy [22], whereas sermorelin has no currently marketed approval [2].

Feature	Sermorelin	Tesamorelin
Backbone	GHRH(1-29)-NH2	GHRH(1-44)-NH2
N-terminal modification	None	trans-3-hexenoyl on Tyr1 [21]
DPP-4 resistance	No (native Tyr-Ala) [12]	Yes [21]
Molecular weight	3357.9 g/mol [7]	5135.9 Da (free base) [22]
US status	Approved 1990/1997, discontinued 2008 [3]	Approved 2010, marketed [22]
Pivotal evidence	Open-label paediatric GHD studies [15]	Two randomised phase 3 trials, 806 patients pooled [23]
WADA	S2.2.4 [19]	S2.2.4 [19]

The two are often compared online as if interchangeable. They act on the same receptor, but tesamorelin’s approved use rests on placebo-controlled phase 3 data in a specific population, while sermorelin’s clinical record is older, smaller and mostly uncontrolled. See our tesamorelin overview for the trial detail.

Sermorelin vs CJC-1295

CJC-1295 was built on sermorelin’s sequence. Its developers made a tetrasubstituted GRF(1-29) and added a lysine carrying a maleimidopropionyl group at the C-terminus so that the peptide binds covalently to serum albumin; in rats the conjugate stayed in plasma beyond 72 hours [20]. In healthy adults its estimated half-life was 5.8 to 8.1 days [24], against minutes for native GHRH peptides [12].

Feature	Sermorelin	CJC-1295 (with DAC)	Modified GRF(1-29) (“CJC-1295 without DAC”)
Sequence basis	Native GHRH(1-29)	GHRH(1-29) with D-Ala2, Gln8, Ala15, Leu27 plus Lys30(maleimidopropionyl) [20] [25]	Same four substitutions, no Lys30 linker
Albumin binding	No	Yes, covalent at Cys34 of albumin [20]	No
Human half-life	Minutes (parent hormone data) [12]	5.8–8.1 days [24]	No published human value found
Approval history	US approved 1990/1997, discontinued	Never approved; a phase 2 study in HIV patients with visceral obesity was terminated [26]	No approved product

For the chemistry of the two CJC-1295 forms, see our CJC-1295 overview.

How Winhycare Pharma supplies sermorelin

Winhycare Pharma supplies sermorelin as research-use-only material for laboratory work, at a purity of ≥99% as stated in our product brochure, with batch QC documentation. Custom synthesis of GHRH analogues and related sequences is available on request. Specifications and enquiry details are on the sermorelin product page, or you can contact us about research peptides.

For laboratory research use only. Not for human or veterinary use.