Growth Hormone Secretagogues Explained — GHRH Analogues vs Ghrelin Receptor Agonists

Two pathways, one pituitary

The pituitary releases growth hormone (GH) under the control of two counterposed hypothalamic signals: growth-hormone-releasing hormone (GHRH), which stimulates, and somatostatin, which inhibits. In addition, the stomach-derived peptide ghrelin acts on a distinct receptor — the growth hormone secretagogue receptor (GHSR-1a) — on pituitary somatotrophs, also driving GH release.

A "growth hormone secretagogue" is any compound that pushes this system toward GH release. The research peptides in this category fall into two clean mechanistic families:

1. GHRH analogues — sermorelin, CJC-1295, tesamorelin. These are truncated or modified versions of native GHRH(1-44) that bind the pituitary GHRH receptor.
2. Ghrelin receptor agonists (GHRPs) — ipamorelin, GHRP-2, GHRP-6, hexarelin. These are synthetic peptides that act on GHSR-1a, mimicking ghrelin's GH-releasing effect.

The GHRH analogue family

Sermorelin

Sermorelin is GRF(1-29), the N-terminal 29 amino acids of native GHRH — the minimum active fragment. It has a short plasma half-life (minutes) and historically had drug approval in some jurisdictions for paediatric growth hormone deficiency. It is not currently marketed as an approved drug in Canada.

CJC-1295

CJC-1295 is a modified GHRH(1-29) analogue with four amino acid substitutions that confer protease resistance and, in one variant, a lysine residue that enables covalent binding to serum albumin via a maleimide linker — extending plasma half-life from minutes to days. Teichman et al. (JCEM 2006) reported sustained elevations of GH and IGF-1 in healthy volunteers after single injections of the albumin-binding variant ("CJC-1295 with DAC"). The non-DAC variant ("modified GRF 1-29") has a shorter half-life closer to native GHRH.

CJC-1295 is not approved as a drug in any jurisdiction. In Canada it is sold only as a research chemical.

Tesamorelin

Tesamorelin is a stabilised GHRH(1-44) analogue (with an N-terminal trans-3-hexenoyl modification). It is the only GH secretagogue peptide with a Health Canada Notice of Compliance, approved as Egrifta for the reduction of excess abdominal fat in HIV-infected patients with lipodystrophy. The pivotal evidence comes from Falutz et al. (NEJM 2007), which reported significant visceral adipose tissue reduction in randomised placebo-controlled trials.

Tesamorelin's approval is narrow — HIV-associated lipodystrophy — and is not a generic "muscle recovery" or "anti-ageing" indication.

The ghrelin receptor agonist family

Ipamorelin

Ipamorelin is a pentapeptide selective ghrelin receptor agonist, developed by Novo Nordisk and first characterised by Raun et al. (European Journal of Endocrinology 1998). Its defining property is selectivity: in preclinical studies, ipamorelin releases GH without meaningfully elevating cortisol, prolactin, or ACTH — a cleaner profile than the earlier GHRPs. This is the reason ipamorelin is typically the GHSR agonist of choice in current research peptide literature.

GHRP-2

GHRP-2 (pralmorelin) is a hexapeptide ghrelin receptor agonist with more potent GH release than ipamorelin in some models, but with measurable elevations of cortisol and prolactin. It has been studied as a diagnostic tool for growth hormone deficiency in some jurisdictions but is not approved as a drug in Canada.

GHRP-6

GHRP-6 is the original "growth hormone releasing peptide" hexapeptide. It is notable for a pronounced appetite-stimulating effect mediated by central ghrelin signalling — a feature, not a bug, in the hypothalamic research it was originally developed for, but an off-target effect in a GH-release context. Cortisol and prolactin elevations are similar in scale to GHRP-2.

The stacking rationale

The reason CJC-1295 and ipamorelin are discussed together is the mechanistic argument that combining a GHRH analogue with a ghrelin receptor agonist produces additive or synergistic GH release compared with either alone. The two drugs act on different receptors on the same somatotroph — GHRH receptor (Gs-coupled) and GHSR-1a (Gq-coupled) — and the downstream signalling is non-redundant. Preclinical data support this additive picture, though the clinical relevance in humans is not established for non-approved combinations.

"CJC-1295 + ipamorelin" is therefore a mechanistic pairing in research literature, not a Health Canada approved therapy.

Health Canada status, in one table

For the non-approved compounds, Canadian supply is governed by the research-chemical framework: per-batch HPLC, domestic shipping, research-use framing, no therapeutic claims. See the individual encyclopedia entries for CJC-1295, ipamorelin, and tesamorelin.

Summary

Growth hormone secretagogues split cleanly into GHRH analogues and ghrelin receptor agonists, acting on distinct pituitary receptors. Ipamorelin is the most selective agent in its class; CJC-1295 is the long-acting GHRH analogue of current interest; tesamorelin is the only Health Canada approved peptide in the category, and only for HIV lipodystrophy. Everything else in the category — in Canada — is a research chemical for non-clinical laboratory use only.