Sermorelin

GHRH is a 44-amino-acid hypothalamic hormone; its first 29 residues carry the full biological activity, and that fragment, amidated, is sermorelin. Everything else in this group — tesamorelin, CJC-1295, the various "modified GRF(1-29)" products — is a chemically stabilised version of this molecule.

Acute pharmacology. In 30 healthy men, an intravenous dose as low as 0.25 ug/kg released significant growth hormone, with the maximum response at 1-2 ug/kg. Although the peptide itself was cleared within minutes, growth hormone stayed elevated for about three hours [1]. An earlier dose-response study of the closely related [Nle27]GHRH(1-29) compared routes directly: growth hormone rose within 5 minutes intravenously and 10 minutes subcutaneously or nasally, peaked by 30 minutes and was back near baseline at 2 hours. A tenfold higher subcutaneous dose, and a thirtyfold higher nasal dose, were needed to approach the intravenous effect [5].

As a treatment for short stature. Forty-three prepubertal children with growth hormone deficiency of hypothalamic origin were randomised to GHRH(1-29) 30 ug/kg/day, 60 ug/kg/day, or recombinant growth hormone for six months. Height velocity rose by at least 2 cm/year in all but two children. The high-dose GHRH group matched the growth hormone group on height velocity, but only the growth hormone group gained height relative to bone age [3]. A smaller German study was blunter: in seven children, six months of 4-6 ug/kg twice daily failed to improve growth rate in five of them, and switching to daily growth hormone improved it in all, to a mean of 8.5 cm/year. Its authors concluded GHRH could not be recommended for routine treatment [2].

Nasal and continuous dosing. A nasal formulation given three times daily to eight children produced clear growth hormone peaks on day 1, but the peaks shrank by six weeks and further by six months, three children developed GHRH antibodies, and most reported sneezing, runny nose and mucosal burning; the conclusion was that it was unsuitable in that form [6]. Continuous subcutaneous infusion in six children produced a biphasic pattern: 24-hour growth hormone output roughly doubled early, then fell below baseline by six months, with one child's secretion suppressed completely [7].

Sermorelin was withdrawn from the US market, and no trial has studied it in healthy adults — for muscle, fat, sleep, ageing or anything else.

Sermorelin binds the GHRH receptor on pituitary somatotrophs, which raises cAMP and releases stored growth hormone. Because the signal enters the axis at its physiological point, secretion remains pulsatile and IGF-1 feedback and somatostatin tone still operate. Its practical weakness is that dipeptidyl peptidase-IV cleaves it within minutes [8], giving a half-life of about 4.3 minutes [4]. Every subsequent GHRH analogue is an attempt to fix that: a D-Ala2 substitution alone nearly halves metabolic clearance [4], and albumin conjugation stretches the half-life to days [9].

GHRH signalling is also tied to sleep. Pulsatile GHRH increases slow-wave sleep, and blocking endogenous GHRH receptors with an antagonist in healthy men suppressed nocturnal growth hormone — but left slow-wave sleep intact, which dissociates the two [10]. That is worth knowing before assuming a GHRH analogue will improve deep sleep.

Sermorelin acetate is GHRH(1-29)-NH2, a 29-residue amidated peptide. Studied by intravenous, subcutaneous and nasal routes; nasal bioavailability is about 3-5% [1]. It is not currently marketed in the United States, so material sold under the name comes from compounding pharmacies or unregulated suppliers [11].

Sermorelin was a licensed drug, and the paediatric studies report it as generally well tolerated by injection [3]. The nasal formulation was not: most children had sneezing, rhinorrhoea and mucosal burning, and treatment was stopped in two of eight [6].

The notable pharmacological problems are loss of effect and immunogenicity with sustained use. Nasal dosing produced shrinking growth hormone peaks over six months and GHRH antibodies in three of eight children [6]; continuous subcutaneous infusion drove 24-hour growth hormone output below baseline by six months [7]. There is no safety data at all in healthy adults, and none for long-term use outside growth hormone deficiency.

GHRH and the ghrelin-receptor peptides are strongly synergistic on growth hormone release, and that synergy requires an intact hypothalamus [12]. Low-dose GHRH with a GH-releasing peptide is sensitive enough to serve as a diagnostic test for adult growth hormone deficiency [13]. No interactions with other compounds on this site have been documented.