Sermorelin

Research summary

Sermorelin is GHRH(1-29)NH2: the first 29 amino acids of human growth hormone-releasing hormone with a C-terminal amide, the shortest synthetic fragment that keeps the full biological activity of the native 44-residue hormone¹. As sermorelin acetate (Geref), it was FDA-approved as a pituitary diagnostic in 1990 and for idiopathic growth hormone deficiency in children in 1997; the manufacturer discontinued both products in 2008, and FDA later found they were not withdrawn for reasons of safety or effectiveness. The peptide sold here is for laboratory research only.

Also known as

GHRH (1-29) NH2 · GRF 1-29 · Sermorelin acetate · Geref

Sequence

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

What is sermorelin?

Growth hormone-releasing hormone (GHRH) was characterized in 1982 by two groups working from pancreatic tumors that produced it; one tumor had caused acromegaly, and the peptide isolated from it was 44 amino acids long^2,3. Sermorelin is the first 29 residues of that sequence, amidated at the C terminus, and it specifically stimulates growth hormone (GH) secretion from the anterior pituitary¹.

It acts at the GHRH receptor, a G protein-coupled receptor expressed predominantly, if not exclusively, in the anterior pituitary, which binds GHRH with high affinity and signals through cyclic AMP⁴.

Is sermorelin FDA-approved? The Geref history

According to FDA's March 2013 notice in the Federal Register, sermorelin acetate was marketed as Geref by EMD Serono under two applications. A diagnostic product, approved on December 28, 1990, was indicated for evaluating the ability of the pituitary somatotroph to secrete GH. A second product, approved on September 26, 1997, was indicated for idiopathic GH deficiency in children with growth failure.

In 2008 EMD Serono told FDA that both products were being discontinued and asked for the applications to be withdrawn; FDA withdrew approval of both effective June 18, 2009. In 2013, responding to a citizen petition, FDA determined that neither Geref product had been withdrawn from sale for reasons of safety or effectiveness. The notice does not give the company's business reasons.

What the clinical research measured

In the open-label Geref International Study Group trial, 110 previously untreated prepubertal children with GH deficiency received GHRH(1-29) for up to a year. In the 86 eligible for efficacy analysis, mean height velocity rose from 4.1 cm per year at baseline to 8.0 at six months and 7.2 at twelve months, without excessive IGF-I generation or changes in fasting glucose⁵.

A 1999 review concluded that intravenous sermorelin was a rapid and relatively specific diagnostic test for GH deficiency, although a normal response could not rule out deficiency of hypothalamic origin. It noted that height-velocity gains were smaller than with somatropin in indirect comparisons, and that transient facial flushing and local reactions at the administration site were the most common adverse events¹.

In adults, a 1992 study at the National Institute on Aging gave GHRH(1-29) for 14 days to 10 healthy older men. At the higher of two amounts tested, mean 24-hour GH, GH peak amplitude and IGF-I rose to levels no longer different from those of young men, with no change in fasting glucose⁶. That was a short hormone-level study, not a test of clinical outcomes.

Why native GHRH(1-29) is short-lived

In human plasma, dipeptidyl peptidase IV cuts GHRH, including the 1-29 fragment, between residues 2 and 3; a D-amino acid at position 1 or 2 prevents this⁷. The resulting fragment has less than one-thousandth of the original activity, and intact GHRH(1-44) had a half-life of about 6.8 minutes after intravenous administration in people⁸. The corresponding sermorelin metabolite, GHRH(3-29), has been detected in human plasma by anti-doping methods⁹.

Later analogues such as CJC-1295 without DAC and tesamorelin carry N-terminal modifications intended to resist this breakdown. See CJC-1295 with DAC vs without DAC and Ipamorelin vs Sermorelin vs Tesamorelin for comparisons.

Limitations of the evidence

• Most clinical data date from the late 1980s and 1990s and concern diagnostic testing and GH-deficient children^1,5.
• Studies in adults were small and short, with hormone levels rather than clinical outcomes as endpoints⁶.
• A 2018 review of GH secretagogues found few long-term, rigorously controlled studies and flagged possible rises in blood glucose through reduced insulin sensitivity as a concern for the class¹⁰.
• Research-grade sermorelin is not the discontinued Geref drug product; its identity and purity rest on testing. Every Peptides Only lot ships with a lot-matched certificate of analysis (HPLC purity and mass-spec identity) from an independent lab, published at our COA library.

Further reading

• CJC-1295 With DAC vs Without DAC (Mod GRF 1-29): How the Research Compares
• Ipamorelin vs Sermorelin vs Tesamorelin: How the Research Compares