Sermorelin

Sermorelin is a synthetic copy of the first 29 amino acids of human growth hormone-releasing hormone (GHRH), finished with a C-terminal amide. This listing is the 10 mg vial of freeze-dried powder, the main fill in a range that also includes a 5 mg vial. Published work on sermorelin covers how it drives growth hormone release from the pituitary, its clinical use as a diagnostic test and growth treatment in children, short studies in older men, and the ways it breaks down in water.

Sequence, mass and molar amount

The lot certificate gives the sequence as H-YADAIFTNSYRKVLGQLSARKLLQDIMSR-NH₂. Those 29 residues are identical to positions 1 to 29 of the 44-residue hormone that Guillemin's group sequenced in 1982¹; sermorelin simply stops at arginine 29 and carries an amide where the chain was cut. The theoretical mass is 3357.9 Da, and the LC-MS identity figure on the certificate is the number to compare with it.

From the stated mass, 10 mg of sermorelin is about 3.0 µmol. The real figure is a little lower because the powder also holds the residual water the certificate reports. For how sermorelin sits beside the other GHRH analogues and the ghrelin-receptor peptides, see sermorelin vs ipamorelin vs tesamorelin.

What the research covers

Where sermorelin comes from

GHRH was first isolated in 1982 from a human pancreatic tumour that had caused acromegaly. Guillemin and colleagues reported a 44-residue amidated peptide whose synthetic copy was fully active in vitro and in vivo and acted specifically on growth hormone secretion¹. Sermorelin is the 29-residue analogue of that hormone, described in a 1999 review as the shortest synthetic peptide with the full biological activity of GHRH². By both routes the review covered, it stimulated growth hormone secretion specifically from the anterior pituitary².

Clinical studies in children

Most of the human evidence comes from paediatric endocrinology. Prakash and Goa reviewed sermorelin as a diagnostic test and found it a rapid, fairly specific test for growth hormone deficiency, with fewer false positives than other provocative tests². They also noted its limit: a normal response cannot rule out deficiency of hypothalamic origin, so other tests are still needed². As a treatment, the Geref International Study Group ran an open-label multicentre study in 110 previously untreated prepubertal children with growth hormone deficiency³. Mean height velocity rose from 4.1 cm a year at baseline to 8.0 at six months and 7.2 at twelve months, 74% of children were judged good responders at six months, and bone age advanced in step with height age³. No adverse changes in blood chemistry, fasting glucose or IGF-I were seen³. The review added that growth responses were smaller than those reported with somatropin, although the two had not been compared head to head, and that transient facial flushing and local pain were the adverse events reported most often².

A short study in older men

Corpas and colleagues compared ten healthy men aged about 68 with nine young men. At baseline the older men had lower IGF-I and shorter growth hormone peaks; after two weeks of GHRH(1-29) at the higher of two amounts tested, 24-hour growth hormone output and IGF-I no longer differed between the age groups⁴. Fasting glucose, blood pressure and routine blood chemistry were unchanged⁴.

Chemistry in solution

Two residues near the N-terminus decide how long sermorelin lasts once dissolved. Bongers and colleagues isolated the breakdown products of GRF(1-29)-NH₂ in water: below about pH 4 the chain is cut between Asp3 and Ala4, leaving GRF(4-29)-NH₂, while above pH 4 Asp3 mostly isomerises to beta-aspartate⁵. At pH 5 and higher, Asn8 deamidates to beta-Asp8 and Asp8 in roughly a 4:1 ratio⁵. Every product they tested had much lower in vitro potency than the intact peptide, and the chain was most stable between pH 4 and 5⁵. Working with a related GRF analogue at pH 7.4 and 37 °C, Friedman's group found the Asn8 route dominant and measured the beta-Asp8 product as 400 to 500 times less potent in pituitary cells⁶.

What is not established

The older-men study ran for two weeks in ten people and measured hormones only. Its authors suggested that longer treatment might change body composition, but the study did not test that⁴. In children, the effect of long-term treatment on final adult height had not been determined when the 1999 review was written². The sermorelin research guide covers the wider literature.

Frequently asked questions

References

1. Guillemin R, Brazeau P, Böhlen P, et al. Growth hormone-releasing factor from a human pancreatic tumor that caused acromegaly. Science. 1982;218(4572):585-7. DOI · PubMed
2. 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):139-57. DOI · PubMed
3. Thorner M, Rochiccioli P, Colle M, et al. Once daily subcutaneous growth hormone-releasing hormone therapy accelerates growth in growth hormone-deficient children during the first year of therapy. Geref International Study Group. J Clin Endocrinol Metab. 1996;81(3):1189-96. DOI · PubMed
4. Corpas E, Harman SM, Piñeyro MA, et al. Growth hormone (GH)-releasing hormone-(1-29) twice daily reverses the decreased GH and insulin-like growth factor-I levels in old men. J Clin Endocrinol Metab. 1992;75(2):530-5. DOI · PubMed
5. Bongers J, Heimer EP, Lambros T, et al. Degradation of aspartic acid and asparagine residues in human growth hormone-releasing factor. Int J Pept Protein Res. 1992;39(4):364-74. DOI · PubMed
6. Friedman AR, Ichhpurani AK, Brown DM, et al. Degradation of growth hormone releasing factor analogs in neutral aqueous solution is related to deamidation of asparagine residues. Replacement of asparagine residues by serine stabilizes. Int J Pept Protein Res. 1991;37(1):14-20. DOI · PubMed