Sermorelin is the synthetic 29-residue N-terminal fragment of human growth hormone releasing hormone, written across the endocrinology literature as GHRH(1-29) or GRF 1-29. It is one of the oldest and most thoroughly characterised GHRH analogues, which is why it appears so often as a reference compound in somatotropic axis research. This overview covers the receptor pharmacology, the sequence rationale and the published reference literature, with citations at the end. No therapeutic claim is made here and no administration guidance is given.
The sequence and why it is truncated
Endogenous human GHRH is a 44-amino-acid hypothalamic peptide. Structure-activity work in the 1980s established that the determinants of activity sit in the N-terminal portion of the molecule. In rat pituitary cells in culture, Ling et al. (1984) found that the amidated 1 to 29 fragment kept about half the potency of the full-length hormone, and that activity disappeared only when the chain was cut back to 19 residues. Sermorelin is that 1 to 29 fragment, usually presented as the C-terminal amide, GHRH(1-29)NH2, and Prakash and Goa (1999) describe it as the shortest synthetic peptide with the full biological activity of GHRH.
The practical consequence for laboratory work is that sermorelin is a synthesis-accessible linear peptide rather than a full-length hypothalamic hormone, while still functioning as a GHRH receptor agonist in published pharmacology. That is the basis on which it entered clinical investigation as a diagnostic and research agent.
GHRH receptor pharmacology
The GHRH receptor (GHRHR), whose human form was cloned from pituitary tissue by Gaylinn et al. (1993), is a class B secretin-family G-protein-coupled receptor expressed principally on anterior pituitary somatotrophs. In the published literature, agonist engagement couples through Gs to adenylate cyclase, raising intracellular cyclic AMP, which is the signalling step associated with growth hormone synthesis and release from those cells. Because they act on the pituitary's own receptor, upstream of growth hormone release, rather than replacing its output, GHRH analogues are described in the literature as acting within the existing hypothalamic-pituitary feedback architecture, including negative regulation by somatostatin.
That distinction, receptor-level stimulation of an endogenous axis versus exogenous replacement, is the main reason sermorelin and other GHRH analogues are studied separately from recombinant growth hormone in the research literature. It is a mechanistic distinction, not a claim of comparative benefit.
Published reference literature
Vance et al. (1986) studied intravenous, subcutaneous and intranasal administration of the GHRH analogue [Nle27]GHRH(1-29)-NH2 in healthy men, in Clinical Pharmacology and Therapeutics, one of the early characterisations of a truncated analogue across routes. Brain et al. (1990) reported continuous subcutaneous GHRH(1-29)NH2 in short, slowly growing children in Clinical Endocrinology, and Kirk et al. (1994) published a further study in children with idiopathic short stature in the same journal. Vittone et al. (1997) examined single nightly injections of GHRH 1-29 in healthy elderly men in Metabolism.
The compound itself was reviewed by Prakash and Goa in BioDrugs in 1999 under the title "Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency". Walker (2006) published a later commentary in Clinical Interventions in Aging. Achermann et al. (2000) reported on the growth hormone response to low-dose bolus GHRH(1-29)NH2 in adults with growth hormone insufficiency after cranial irradiation, in European Journal of Endocrinology, work that is relevant where the fragment is used as a pituitary probe rather than as an intervention.
Outcome figures from those studies are deliberately not reproduced here. Where a specific number matters to a research design, the primary paper should be read directly; the references below carry the PubMed links needed to retrieve them.
Sermorelin compared with tesamorelin
Tesamorelin is the other GHRH analogue Peptx stocks, and the two are frequently confused. Tesamorelin is described in its published programme as a growth hormone releasing factor analogue: the GHRH backbone carrying an N-terminal trans-3-hexenoyl modification intended to improve stability against dipeptidyl peptidase degradation. In non-clinical work the modified peptide resisted dipeptidyl peptidase-4 and broke down more slowly than natural GHRH in plasma, as reported by Ferdinandi et al. (2007). It has a distinct clinical record, principally Falutz et al. (2010), a pooled analysis of two phase 3 trials in the Journal of Clinical Endocrinology and Metabolism, and Stanley et al. (2014) in JAMA, both in HIV-associated abdominal fat accumulation, plus Stanley et al. (2019) in Lancet HIV, in people with HIV and non-alcoholic fatty liver disease.
At the receptor level both are GHRH receptor agonists. The difference reported in the literature is structural stabilisation and, consequently, a different pharmacokinetic profile and a different clinical development history. That is a mechanism-level statement only, and no superiority is implied in either direction.
Related pages
- Sermorelin single vial, UK Express stock
- Buy sermorelin in the UK
- Buy tesamorelin in the UK
- Tesamorelin single vial
References
- Achermann JC, et al. (2000). The GH response to low-dose bolus growth hormone-releasing hormone (GHRH(1-29)NH2) is attenuated in patients with longstanding post-irradiation GH insufficiency. European Journal of Endocrinology. PubMed 10754477
- Brain CE, et al. (1990). Continuous subcutaneous GHRH(1-29)NH2 promotes growth over 1 year in short, slowly growing children. Clinical Endocrinology. PubMed 2140733
- Falutz J, et al. (2010). Effects of tesamorelin (TH9507), a growth hormone-releasing factor analog, in human immunodeficiency virus-infected patients with excess abdominal fat: a pooled analysis of two multicenter, double-blind placebo-controlled phase 3 trials with safety extension data. Journal of Clinical Endocrinology and Metabolism. PubMed 20554713
- Ferdinandi ES, et al. (2007). Non-clinical pharmacology and safety evaluation of TH9507, a human growth hormone-releasing factor analogue. Basic & Clinical Pharmacology & Toxicology. PubMed 17214611
- Gaylinn BD, et al. (1993). Molecular cloning and expression of a human anterior pituitary receptor for growth hormone-releasing hormone. Molecular Endocrinology. PubMed 7680413
- Kirk JM, et al. (1994). Treatment with GHRH(1-29)NH2 in children with idiopathic short stature induces a sustained increase in growth velocity. Clinical Endocrinology. PubMed 7955460
- Ling N, et al. (1984). Synthesis and in vitro bioactivity of C-terminal deleted analogs of human growth hormone-releasing factor. Biochemical and Biophysical Research Communications. PubMed 6435620
- Prakash A, Goa KL. (1999). Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency. BioDrugs. PubMed 18031173
- Stanley TL, et al. (2014). Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation: a randomized clinical trial. JAMA. PubMed 25038357
- Stanley TL, et al. (2019). Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial. The Lancet HIV. PubMed 31611038
- Vance ML, et al. (1986). The effect of intravenous, subcutaneous, and intranasal GH-RH analog, [Nle27]GHRH(1-29)-NH2, on growth hormone secretion in normal men: dose-response relationships. Clinical Pharmacology and Therapeutics. PubMed 3096623
- Vittone J, et al. (1997). Effects of single nightly injections of growth hormone-releasing hormone (GHRH 1-29) in healthy elderly men. Metabolism. PubMed 9005976
- Walker RF. (2006). Sermorelin: a better approach to management of adult-onset growth hormone insufficiency? Clinical Interventions in Aging. PubMed 18046908
Research use only. Sermorelin is supplied by Peptx strictly as laboratory reference material and is not for human or animal consumption.