THE GH AXIS EXPLAINED
How Growth Hormone Secretagogues Work — GHRH, Ghrelin, Pulses, and IGF-1
By G1 Peptides · Medically reviewed by the G1 Peptides clinical team · Updated September 24, 2026 · 3 min read
THE SHORT ANSWER
Growth hormone is released by the pituitary in pulses, mostly during deep sleep, under two signals — GHRH says "release" and ghrelin amplifies it. Secretagogue peptides are copies of those signals: sermorelin, CJC-1295, and tesamorelin mimic GHRH; ipamorelin mimics ghrelin. Because they trigger your own pituitary rather than adding external hormone, the body's feedback loops stay intact — which is the main argument for them over HGH itself.
The axis in three steps
- Hypothalamus releases growth-hormone-releasing hormone (GHRH) — the "go" signal — and, between pulses, somatostatin — the "stop" signal.
- Pituitary somatotroph cells respond to GHRH by releasing growth hormone in a burst. A second input, ghrelin (the "hunger hormone," acting on the GHS-R receptor), amplifies the burst and suppresses somatostatin.
- Liver and tissues respond to GH by producing IGF-1, which drives most of the downstream effects — protein synthesis, lipolysis, collagen turnover, tissue repair — and feeds back to shut the axis off.
GH is not released steadily. It comes in pulses, roughly every three to four hours, with the biggest by far in the first ninety minutes of slow-wave sleep. Pulse size declines steadily with age — by the fifties, total daily GH output is a fraction of what it was at twenty (Walker 2006).
Where each peptide acts
| Peptide | Mimics | Receptor | Half-life | Character |
|---|---|---|---|---|
| Sermorelin | GHRH (1–29) | GHRH-R | ~10–20 min | Short, physiological pulse |
| CJC-1295 (no DAC) / Mod GRF 1-29 | GHRH, stabilized | GHRH-R | ~30 min | Stronger pulse, still pulsatile |
| CJC-1295 with DAC | GHRH, albumin-bound | GHRH-R | ~6–8 days | Sustained elevation, less pulsatile |
| Tesamorelin | GHRH, stabilized | GHRH-R | ~30 min | Potent; FDA-approved |
| Ipamorelin | Ghrelin | GHS-R (ghrelin receptor) | ~2 h | Selective — no cortisol or appetite rise |
The GHRH mimics tell the pituitary to release; the ghrelin mimic makes the release bigger and quiets somatostatin. That is why a GHRH analog is almost always paired with a GHRP: two receptors, one pulse, more GH than either alone. CJC-1295/ipamorelin is the canonical pairing — the Apex blend at G1.
Why ipamorelin specifically
Earlier ghrelin mimics — GHRP-6, GHRP-2, hexarelin — released GH but also raised cortisol and prolactin and, through the ghrelin receptor, caused intense hunger. Ipamorelin was the first secretagogue shown to release GH selectively without those effects (Raun 1998). That selectivity is why it is the GHRP of choice in nearly every modern protocol.
Secretagogues versus HGH
Injected somatropin delivers a fixed amount of hormone regardless of what the pituitary or IGF-1 feedback would prefer. It works — and it is approved for true deficiency — but it flattens the pulsatile pattern and carries dose-related risks (fluid retention, glucose effects, carpal tunnel) that scale with the amount injected.
Secretagogues can only release what the pituitary can produce, and the IGF-1 feedback loop still applies. The ceiling is lower, but so is the risk, and the pattern stays pulsatile — which matters for how tissues respond. For adults with age-related decline rather than true deficiency, that trade is usually the right one.
Timing and food
GH release is blunted by insulin and by fatty acids in the blood, so secretagogues are dosed away from meals — bedtime, fasted, is the default. Some protocols add a morning or post-training dose. Alcohol suppresses the sleep pulse and is the most common reason a protocol underperforms.
Next: the secretagogues compared.
FREQUENTLY ASKED
Are secretagogues the same as taking HGH?
No. HGH (somatropin) is the hormone itself, injected at fixed doses that override the pituitary. Secretagogues prompt the pituitary to release its own GH in physiological pulses, subject to normal feedback. The effect is generally smaller and the safety profile more forgiving.
What does IGF-1 have to do with it?
Growth hormone tells the liver to make insulin-like growth factor 1, which carries out most of GH's tissue effects. Because GH itself pulses and is hard to measure, providers track IGF-1 as the steady readout of how much GH signalling is happening.
Why bedtime?
The largest natural GH pulse occurs in the first hours of deep sleep. Dosing a secretagogue before bed adds to that pulse instead of fighting the daytime rhythm, and fasting before bed removes the blunting effect of food.
SOURCES
This article is educational and is not medical advice. Peptides are prescription medications; whether any of them is appropriate for you is a decision for a licensed provider who knows your history.