How growth hormone release is controlled
Growth hormone is not secreted at a steady rate. The pituitary releases it in bursts, largest in the hours after sleep onset, with concentrations falling close to zero in between. Three signals set that rhythm. Growth-hormone-releasing hormone (GHRH) from the hypothalamus turns secretion on. Somatostatin, also hypothalamic, turns it off, and the alternation between the two produces the pulses. Ghrelin, made mainly in the stomach, acts as a third input through its own receptor and amplifies the bursts.
Downstream, growth hormone acts on the liver and other tissues to raise IGF-1, which in turn feeds back on the hypothalamus and pituitary to damp secretion. The loop matters for anything in this guide, because every compound described here works inside it rather than around it. Injected recombinant growth hormone overrides the system. A secretagogue asks the pituitary to release more of its own, which means the ceiling is set by the gland and the feedback stays live.
Two families of secretagogue
The peptides sold as growth hormone secretagogues fall into two groups that are easy to confuse, because they are marketed together and often sold in one vial. They act on different receptors and behave differently.
The first group are the ghrelin-receptor agonists, usually called GHRPs. They bind GHS-R1a, the receptor for ghrelin, which sits both on pituitary somatotrophs and on hypothalamic neurons. They push stored growth hormone out and simultaneously lower somatostatin tone, releasing the brake. The oldest of them was designed before anyone knew the receptor existed: GHRP-6 was built in the early 1980s from opioid peptide fragments, the receptor was identified in 1996, and ghrelin itself was described in 1999.
The second group are the GHRH analogues. They copy the body's own releasing hormone, with modifications that stop enzymes destroying it within minutes. They act only on the GHRH receptor, so they raise growth hormone synthesis as well as release, and the shape of their effect depends entirely on how long they last. Because the two families use separate pathways, most research combinations pair one from each.
The ghrelin-receptor agonists compared
Four peptides in this family turn up repeatedly in the literature and in supplier catalogues. Relative potency is given qualitatively on purpose: published comparisons use different species, routes and endpoints, and a single number would imply a precision that does not exist.
| Peptide | GH release | Cortisol and prolactin | Appetite | Response over time | Status |
|---|---|---|---|---|---|
| Ipamorelin | In the range of GHRP-6 in the original swine work | No meaningful rise in swine, even far above the GH dose | Not a prominent finding in published work | Not well characterised | Reached phase 2; never approved |
| GHRP-2 | Stronger than GHRP-6 on a milligram basis | Small, dose-related rises | Food intake about a third higher in a small human study | Class attenuation reported | Diagnostic agent in Japan; no treatment approval |
| GHRP-6 | The reference compound the others are measured against | Small rises reported | Pronounced | Class attenuation reported | Research compound; never approved |
| Hexarelin | Among the most potent of the group | Small rises reported | Not well characterised | Partial, reversible loss of response with prolonged dosing | Investigational; never approved |
Two columns carry most of the information. The cortisol and prolactin column explains why ipamorelin exists at all: the receptor is not specific to growth hormone, and the older peptides move other pituitary outputs with it. Raun and colleagues reported in 1998 that ipamorelin released growth hormone in pigs with no meaningful ACTH or cortisol response even at doses more than 200-fold above the effective one, which is the single result that built its reputation. It is animal evidence, and it has never been mapped out to the same extent in people.
The appetite column is the mirror image. GHRP-6 is strongly orexigenic, which is a problem in a metabolic experiment and the entire point in a model of appetite regulation. Hexarelin is the outlier in the last column: it also binds the scavenger receptor CD36, and repeated dosing in human studies partly blunts the growth hormone response.
The GHRH analogues compared
This group is smaller and the differences are simpler: they come down to how long the molecule survives.
| Compound | What it is | Duration of action | Status |
|---|---|---|---|
| CJC-1295 with DAC | GHRH(1-29) with four substitutions plus an albumin-binding linker | ≈ 6–8 days | Development discontinued; no approval |
| CJC-1295 without DAC (Mod GRF 1-29) | The same modified fragment, without the linker | Minutes | No approval; no dose-ranging trial published under this name |
| Tesamorelin | Full GHRH(1-44) with a trans-3-hexenoyl group at the N-terminus | ≈ 26–38 minutes | Approved in the US as Egrifta; not authorised in the EU |
| Sermorelin | Plain GHRH(1-29), the original unmodified fragment | Minutes | Older GHRH medicine, not currently marketed in the EU |
The gap between the first two rows is the most consequential fact in this guide, and the two forms share a name. In the phase 1 study by Teichman and colleagues in 2006, one subcutaneous dose of the DAC version raised growth hormone 2- to 10-fold for six days or more and IGF-1 for 9 to 11 days. That is a sustained elevation, not a pulse. The version without the linker produces a single burst and disappears. Whether a continuous signal or an extra pulse is the better model depends on the question being asked, and no trial has compared them for a clinical outcome.
Tesamorelin is the only compound in either table with a licensed medicine behind it. Its trials in HIV-associated abdominal fat used 2 mg once daily for 26 weeks and reported a reduction in visceral fat of roughly 15%, with IGF-1 monitored throughout. It is approved in the United States and has no EU marketing authorisation.
Why the two families are studied together
Give a GHRH analogue and a GHRP at the same time and the growth hormone response is larger than either produces alone. This has been reported in human studies since the 1990s, and the reason is mechanical rather than mysterious: the GHRH analogue raises cyclic AMP inside the somatotroph and drives synthesis, while the GHRP triggers release through a calcium-dependent pathway and lowers the somatostatin brake at the same time. Two levers, one cell.
That combined effect is why blended vials exist, and why almost all of the pairing literature uses one peptide from each family. It also explains a limitation. A larger pulse is a pharmacological result, not a clinical one. No controlled trial has shown that the combination changes body composition, tendon healing or performance in people, and a supplier page implying otherwise is describing an expectation rather than data.
Measuring GH and IGF-1 in research
Hormone read-outs are where most amateur claims about this class fall apart, because a single blood draw for growth hormone is close to meaningless. Between pulses the concentration is near zero in a perfectly healthy person. Published work therefore uses one of a handful of approaches.
- Frequent sampling. Blood drawn every 10 to 20 minutes for 12 or 24 hours, then summarised as area under the curve or broken into pulse number, amplitude and frequency.
- Provocation testing. A stimulus is given and the peak response measured over the following hour. The insulin tolerance test is the classical reference; arginine, glucagon, GHRH and ghrelin-receptor agonists are all used as alternatives.
- IGF-1 as an integrated marker. IGF-1 is stable across the day and reflects growth hormone exposure over days, which makes it the practical measure. Results are read against age- and sex-specific reference ranges, usually as a standard deviation score.
Two cautions apply to the numbers that come back. IGF-1 immunoassays are not interchangeable: different platforms give different absolute values, so comparisons belong within one laboratory and one method. And IGF-1 is not a pure growth hormone read-out, since nutritional state and liver function move it as well. Levels also sit at the centre of anti-doping science: injected recombinant growth hormone is a single isoform and is caught by an isoform ratio test, while a secretagogue raises the body's own mixture, so screening in that case leans on markers such as IGF-1 and on direct detection of the peptide. The analogue further down the same axis, IGF-1 LR3, is a research reagent rather than a secretagogue and belongs to a separate discussion.
Status, rules and what the data do not show
None of the four GHRPs has ever been approved as a treatment. GHRP-2 holds a Japanese licence as a diagnostic agent, which is an approval to run a test rather than to treat anyone. Two orally active relatives went further than the injectables: macimorelin is licensed as a diagnostic test for adult growth hormone deficiency, and anamorelin was taken through phase 3 trials in cancer-related weight loss. Among the GHRH analogues, only tesamorelin holds a current approval, and not in Europe.
For competitive athletes the whole subject is closed. Section S2 of the WADA Prohibited List covers growth hormone secretagogues, GHRH analogues, IGF-1 and its analogues, and it applies at all times, in and out of competition. For everyone else the practical summary is short. These peptides reliably raise growth hormone. What follows from that in a human body over months has not been established by controlled trials for any of them, and the honest reading of the literature is that the pharmacology is well described while the outcomes are not.
Frequently asked questions
Which secretagogue releases the most growth hormone? On a milligram basis hexarelin and GHRP-2 sit at the potent end and GHRP-6 at the other, but comparisons across species and routes are loose. Potency is also the wrong question for most research designs, where selectivity and duration matter more.
Why are CJC-1295 and ipamorelin sold in one vial? Because they act on different receptors in the same cell and release more growth hormone together than separately. A blend also means one certificate has to account for two peptides, so read it with both masses in mind.
Does a bigger growth hormone pulse mean more IGF-1? Not proportionally. IGF-1 tracks sustained exposure rather than single peaks, which is why a week-long analogue lifts it for days while a short-acting peptide may barely move it.
Can these peptides be bought legally in Europe? They are sold as research chemicals, not medicines. None of the compounds compared in the tables above is authorised as a medicine in the EU today, none is sold for human use, and rules on possession and personal import differ by member state.
Which of them does King Peptides stock? The CJC-1295 + Ipamorelin Blend 5/5 mg and Tesamorelin 10 mg. GHRP-2, GHRP-6 and hexarelin are not in the catalogue, and the blend is the closest product in the same class rather than a replacement for any of them.
Research use only. Everything on PeptideEuropa.com describes peptides for laboratory research. Nothing here is medical advice. Always comply with the laws that apply in your jurisdiction.