Sermorelin

Sermorelin is the synthetic 29-amino-acid N-terminal fragment of human growth-hormone-releasing hormone, GHRH(1-29)-NH2, with a C-terminal amide. Native GHRH is a 44-residue hypothalamic peptide; residues 1–29 were shown to carry the full receptor-activating activity, which is why this fragment became the reference GHRH analog in both research and clinical use. Sermorelin binds the GHRH receptor on pituitary somatotroph cells, a class B G-protein-coupled receptor, and stimulates release of the pituitary's own growth hormone rather than supplying GH directly. Unusually for a research peptide, it has a regulatory history: it was an FDA-approved drug (Geref) for more than a decade [3].

Mechanism and pharmacology

GHRH-receptor activation raises cyclic AMP in somatotrophs, triggering GH synthesis and exocytosis. Because sermorelin acts upstream of the pituitary, GH output remains subject to somatostatin tone and negative feedback from IGF-1, so the secretion pattern retains its pulsatile character. The compound's main pharmacological limitation is stability: Frohman and colleagues showed in 1986 that GHRH is cleaved in plasma by dipeptidyl peptidase IV between Ala2 and Asp3 within minutes, producing an inactive GHRH(3-44) fragment [5]. Sermorelin carries the same unprotected N-terminus, so its circulating half-life is on the order of minutes and its effect is a brief GH pulse. Every later GHRH analog (the CJC-1295 series, tesamorelin) exists chiefly to solve that stability problem.

The Geref record: diagnosis and paediatric treatment

Two forms were approved in the United States: a 0.05 mg ampoule (NDA 19-863, approved December 1990) indicated for testing the pituitary's ability to secrete GH, and 0.5 mg / 1.0 mg vials (NDA 20-443, approved September 1997) indicated for idiopathic growth hormone deficiency in children with growth failure [3]. The pivotal paediatric evidence came from the Geref International Study Group: 110 previously untreated prepubertal GH-deficient children were given 30 µg/kg GHRH(1-29) once daily at bedtime in a multicentre open-label study. Among the 86 evaluable patients, 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; 74% were classed as good responders at 6 months, and bone age advanced in step with height age [1]. A 1999 review in BioDrugs summarised the diagnostic and therapeutic literature, noting that the growth response is generally smaller than that seen with recombinant GH and depends on an intact pituitary [2].

Withdrawal for commercial, not safety, reasons

EMD Serono notified FDA in 2008 that both Geref products were being discontinued and requested withdrawal of the NDAs; FDA withdrew approval effective 18 June 2009. Following a 2012 citizen petition, FDA published a formal determination in March 2013 that Geref was not withdrawn from sale for reasons of safety or effectiveness, having reviewed its files and the post-marketing literature. That determination keeps the products on the Orange Book discontinued list and leaves the door open to generic applications [3]. The practical reading is that recombinant GH captured the paediatric market and Geref stopped being commercially viable, not that a safety signal emerged.

Studies in older adults

The other well-cited dataset is Corpas et al. (1992), which asked whether GHRH(1-29) could restore GH and IGF-1 in older men to young-adult levels. Ten healthy men aged 68 ± 6 years received 0.5 mg and then 1 mg twice daily for 14 days each in a crossover design against nine young controls. At the higher dose, 24-hour mean GH, GH peak area and amplitude, and IGF-1 all rose significantly, to the point that the older group was no longer statistically distinguishable from the young group on those measures [4]. This is a small, short endocrine study, not an outcomes trial. A 2006 editorial in Clinical Interventions in Aging argued the case for GHRH analogs over direct GH in adults on physiological grounds (preserved pulsatility and feedback), while acknowledging that comparative long-term data do not exist [6].

What the research does not establish

The clinical record is specific: paediatric GH deficiency with an intact pituitary, and a diagnostic challenge test. The paediatric trial was open-label and single-arm; the adult study involved ten men for two weeks. No controlled trial has evaluated sermorelin for body composition, recovery, sleep or ageing endpoints in healthy adults, and the 2006 editorial [6] is opinion rather than data. Effects in older adults [4] are hormone-level changes, not functional outcomes. The FDA determination [3] speaks only to why the product left the market; it is not a finding of efficacy for any use beyond the original labelling, and the currently supplied material is not the approved product. This material is supplied strictly for in-vitro laboratory research.

Format. Lyophilized powder in a sealed glass vial. Sermorelin is supplied as the acetate salt; the stated mass refers to the peptide.

Reconstitution. Reconstitute with bacteriostatic water, directing the stream against the glass wall rather than onto the powder cake, then swirl gently until dissolved — do not shake. Our reconstitution calculator converts vial mass and diluent volume into concentration and U-100 syringe units. The N-terminal Ala-Asp bond is susceptible to dipeptidyl-peptidase cleavage, so solutions should not be exposed to serum-containing media before use.

Storage. Lyophilized vials are typically stored at −20 °C and protected from light. Reconstituted solutions are generally refrigerated at 2–8 °C and are less stable than the dry powder; the Asn8 and Met27 residues make the unmodified sequence prone to deamidation and oxidation over time. Aliquot before freezing to avoid repeated freeze-thaw cycles.

Handling. Standard laboratory practice applies: appropriate PPE, aseptic technique when reconstituting, and disposal in line with your institution's procedures. For in-vitro laboratory research only — not for human or veterinary use.