Sermorelin

Sermorelin is a synthetic peptide comprising the first 29 amino acids of endogenous growth hormone-releasing hormone (GHRH). It was FDA-approved in 1997 under the brand name Geref (Serono) for the diagnosis of growth hormone deficiency in children and for GH secretion stimulation tests. The branded product was withdrawn from the US market in 2002 for commercial reasons unrelated to safety or efficacy. It is currently available through licensed compounding pharmacies and is widely used off-label for adult growth hormone insufficiency.

Sermorelin differs from exogenous recombinant human GH (rhGH) in a key way: it stimulates endogenous GH production from the pituitary rather than replacing it. This preserves the hypothalamic-pituitary feedback loop, prevents receptor desensitization, and maintains pulsatile GH secretion — the natural pattern associated with anabolic effects. Sermorelin is WADA-prohibited in competitive sports.

Sermorelin binds the GHRH receptor (GHRHR) on somatotroph cells of the anterior pituitary with full agonist activity. The GHRHR is a class B G protein-coupled receptor coupled to Gαs. Receptor engagement activates adenylyl cyclase → cAMP → PKA → phosphorylation of CREB and other transcription factors → stimulation of GH gene transcription and pulsatile GH secretion.

The 29-amino acid truncation retains full receptor-binding activity: residues 1–29 of GHRH contain the receptor-binding pharmacophore, while the C-terminal residues 30–44 of native GHRH contribute minimally to receptor affinity. Sermorelin's shorter length reduces degradation susceptibility at the C-terminus while preserving full potency.

Critically, sermorelin respects endogenous feedback: somatostatin release from the hypothalamus continues to inhibit GH secretion in a physiologically appropriate manner, preventing the IGF-1 overshoot seen with supraphysiological exogenous GH doses. This feedback preservation is the primary mechanistic argument for preferring sermorelin over rhGH in adult GH insufficiency.