What is Sermorelin?

Compound Spotlight

Sermorelin is the first 29 amino acids of a 44-amino-acid hormone. That shortened chain turned out to carry the hormone’s full growth hormone releasing activity, and it reached the US market as Geref. It later left the market, and the public record documents how.

Where it comes from

The hypothalamic signal that tells the pituitary to release growth hormone was hard to isolate directly. It was first characterized from an unusual source. In 1982, Guillemin and colleagues isolated a 44-amino-acid peptide from a pancreatic tumour that had caused acromegaly in its patient. The tumour was producing the releasing hormone in large amounts, and the synthetic copy had full activity in stimulating growth hormone secretion.

Researchers then looked for the smallest piece that still worked. The answer was the N-terminal 29 residues, with an amide at the C-terminal end. Sermorelin is that fragment, GHRH(1-29)NH2, and it retains the full biological activity of the 44-residue hormone.

How it differs from ipamorelin and the GHRPs

Sermorelin works through the GHRH receptor on pituitary somatotroph cells. It is the “go” signal itself, in shortened form. Ipamorelin, hexarelin and the other GHRPs act on the ghrelin receptor (GHS-R1a), a separate pathway. Our growth hormone secretagogue overview covers how the two families relate.

Among GHRH analogues, sermorelin is the unmodified one. CJC-1295 and tesamorelin were engineered for stability or a longer half-life. Sermorelin keeps the native sequence, so its effect is brief and it relies on a pituitary that is able to respond.

The Geref approvals

According to an FDA notice published in the Federal Register in 2013, sermorelin acetate was approved under the brand name Geref in two forms:

• NDA 19-863, approved December 28, 1990, for evaluating the ability of the pituitary somatotroph to secrete growth hormone (a diagnostic use).
• NDA 20-443, approved September 26, 1997, for the treatment of idiopathic growth hormone deficiency in children with growth failure.

In letters dated July and December 2008, EMD Serono told FDA that both products were being discontinued and asked for the applications to be withdrawn. FDA withdrew approval of both NDAs effective June 18, 2009. In 2013, responding to a citizen petition, FDA determined that neither Geref product was withdrawn from sale for reasons of safety or effectiveness. That determination keeps them on the Orange Book’s Discontinued Drug Product List and allows generic applications to reference them. The notice does not state the company’s commercial reasons for discontinuing.

What the clinical studies examined

Diagnosis. As a test agent, sermorelin was used to probe whether the pituitary could release growth hormone. A 1999 review by Prakash and Goa described it as a rapid and relatively specific test, with fewer false positives than other provocative tests. It had a built-in limitation: a normal response cannot rule out deficiency caused by a hypothalamic problem, because sermorelin bypasses the hypothalamus and acts directly on the pituitary.

Paediatric growth. The pivotal study was an open-label, multicentre trial reported by Thorner and colleagues in 1996. It enrolled 110 previously untreated prepubertal children with growth hormone deficiency, 86 of whom were eligible for efficacy analysis. Mean height velocity rose from 4.1 cm per year at baseline to 8.0 cm per year at six months and 7.2 cm per year at twelve months, with no significant acceleration of bone age relative to height age. There was no untreated control group. The Prakash review noted that effects on final adult height had not been determined, and that sermorelin had not been compared directly with somatropin (recombinant growth hormone) at its recommended regimen. In the indirect comparisons available, height velocity gains were smaller than with somatropin.

Older adults. Researchers also tested it in ageing, on the idea that age-related falls in growth hormone and IGF-I may contribute to the loss of muscle mass and strength. A small study by Vittone and colleagues gave GHRH(1-29) nightly for six weeks to 11 healthy men aged 64 to 76. Nocturnal growth hormone release increased, but IGF-I did not change. Two of six strength measures and one endurance test improved, while body composition and metabolic measures did not change. The authors concluded that single nightly administration was less effective than multiple daily administration at producing growth hormone or IGF-I-mediated effects.

What the evidence supports

Sermorelin has better human evidence than most compounds in its class. It reliably stimulates pituitary growth hormone release in people, and in an open-label trial it increased growth rate in children with growth hormone deficiency. That evidence supported two FDA approvals.

The gaps are real, though. The paediatric data are mostly uncontrolled and from the 1990s, and final-height outcomes were never established. In adults, the published work is small and short, and in the study above it did not raise IGF-I or change body composition. The Geref products are no longer marketed.

Frequently asked questions

Is sermorelin FDA approved?

Not currently. It was approved as Geref in 1990 and 1997. FDA withdrew those approvals in 2009 at the manufacturer’s request, and in 2013 determined that the products were not withdrawn for reasons of safety or effectiveness. No sermorelin product is currently marketed under an active FDA approval.

Is sermorelin the same as CJC-1295?

Both are based on GHRH(1-29). CJC-1295 carries amino acid substitutions for stability, and in its DAC form a chemical group that binds albumin and greatly extends its half-life. Sermorelin is the native sequence without those changes.

Why does sermorelin need a working pituitary?

It does not supply growth hormone. It tells somatotroph cells in the pituitary to release their own. If those cells cannot respond, sermorelin has nothing to act on.

How do I know what is actually in the vial?

Every lot we sell has a published Certificate of Analysis from an independent, third-party lab confirming identity and purity. Lot numbers on the vial should match the COA you are referencing.

References

• Guillemin R, et al. Growth hormone-releasing factor from a human pancreatic tumor that caused acromegaly. Science. 1982;218(4572):585–587.
• Thorner M, et al. Once daily subcutaneous growth hormone-releasing hormone therapy accelerates growth in growth hormone-deficient children during the first year of therapy. J Clin Endocrinol Metab. 1996;81(3):1189–1196.
• Vittone 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.
• 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.
• Food and Drug Administration. Determination that GEREF (sermorelin acetate) injection … were not withdrawn from sale for reasons of safety or effectiveness. Federal Register. 2013;78(42):14095–14096.

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For laboratory and research use only. Not for human consumption. Sermorelin was formerly FDA approved as Geref; those approvals were withdrawn in 2009 at the manufacturer’s request, and no sermorelin product currently holds an active FDA approval. This article summarizes published research for informational purposes and is not medical advice, nor a recommendation or protocol for use.

Related research compounds

Arc Peptides supplies these compounds, each third-party tested for purity and identity with a lot-specific Certificate of Analysis:

• Sermorelin

For laboratory research use only. Not for human consumption.