Explainer
GHRH analogs vs ghrelin mimetics: growth hormone secretagogues explained
Growth hormone secretagogues raise the body’s own GH release rather than replacing GH. They fall into two classes that act on different pituitary receptors: GHRH analogs and ghrelin-receptor agonists. Combining one of each produces more GH than either alone, which is the basis for popular blends.
Two receptors
| GHRH analogs | Ghrelin-receptor agonists (GHS) | |
|---|---|---|
| Receptor | GHRH receptor | GHS-R1a |
| Examples | Sermorelin, tesamorelin, CJC-1295 | Ipamorelin, GHRP-2, GHRP-6, hexarelin, MK-677 |
| Effect on GH pulses | Increases pulse size | Increases pulse size and frequency; counteracts somatostatin |
| Other hormones | Minimal | Some raise cortisol and prolactin (least with ipamorelin) |
| Appetite | No effect | Increases (strongly with GHRP-6 and MK-677) |
| US approval | Tesamorelin (HIV lipodystrophy) | None |
Why feedback matters
Recombinant growth hormone bypasses the pituitary, so the body cannot regulate it. Secretagogues work through the pituitary, which is still subject to somatostatin and IGF-1 feedback. That is why GH levels with secretagogues generally stay closer to physiological ranges, and why researchers have proposed them as a gentler alternative. It also means they need a functioning pituitary to work.
Half-lives
Sermorelin and modified GRF(1-29) last minutes to about half an hour. Ipamorelin and the GHRPs last around two hours. CJC-1295 with DAC binds albumin and lasts about a week, producing sustained IGF-1 elevation. MK-677 is an oral small molecule with a half-life of about a day.
What human data show
- Tesamorelin reduced visceral fat by about 15% in people with HIV lipodystrophy and is FDA-approved for that use.
- CJC-1295 with DAC raised IGF-1 for up to two weeks after a single dose in healthy adults.
- MK-677 increased fat-free mass in older adults over two years, but raised blood sugar and reduced insulin sensitivity.
- Ipamorelin did not improve recovery after bowel surgery in a phase 2 trial.
Related profiles
- GHRH analog Sermorelin Sermorelin is the active 29-amino-acid fragment of growth-hormone-releasing hormone. Approved medicine
- GHRH analog Tesamorelin Tesamorelin is a stabilized form of growth-hormone-releasing hormone. Approved medicine
- Selective ghrelin-receptor agonist Ipamorelin Ipamorelin is a five-residue ghrelin-receptor agonist described in 1998 as the first selective growth hormone secretagogue. Human RCTs
- Multi-peptide blend CJC-1295 + Ipamorelin blend This blend pairs a GHRH analog (usually CJC-1295 without DAC) with the ghrelin-receptor agonist ipamorelin. Animal studies
Questions
Are GH secretagogues the same as HGH?
No. HGH is the hormone itself. Secretagogues signal the pituitary to release more of its own GH.
Are they banned in sport?
Yes. WADA prohibits GH secretagogues, GHRH analogs and ghrelin mimetics under S2.
References
- Teichman SL, Neale A, Lawrence B, et al. (2006). Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults. Journal of Clinical Endocrinology & Metabolism.
- Nass R, Pezzoli SS, Oliveri MC, et al. (2008). Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial. Annals of Internal Medicine.
- Falutz J, Allas S, Blot K, et al. (2007). Metabolic effects of a growth hormone-releasing factor in patients with HIV. New England Journal of Medicine.