The GH Axis: Physiology Behind Secretagogues
GHRH, ghrelin, somatostatin, and pulsatility — why timing rules exist and what long-acting analogs change.
Three levers on one gland
Growth hormone release is a negotiation: hypothalamic GHRH stimulates pituitary somatotrophs, ghrelin amplifies the response through a separate receptor (GHS-R), and somatostatin brakes the system. CJC-1295 imitates GHRH; ipamorelin and MK-677 work the ghrelin receptor. Two levers at once is the mechanistic story behind the popular stack — a story tested in acute pharmacology, not outcome trials.
Pulsatility is the design
Natural GH arrives in pulses, the largest clustering in early deep sleep, with fasting amplifying release and insulin blunting it. That physiology is why "fasted, pre-bed" dosing conventions for secretagogues are at least coherent. It is also why an 8-day-half-life GHRH analog raises a real question: sustained, non-pulsatile elevation is a different physiological state whose long-term effects were never characterized.
Downstream markers
- GH acts largely through hepatic IGF-1, which is why trials track IGF-1 as the axis marker.
- Appetite stimulation is on-target pharmacology for ghrelin agonists — a feature in cachexia research, a bug for fat-loss goals.
- Fasting glucose and insulin sensitivity drift with sustained GH-axis stimulation, the most consequential trade-off in year-long MK-677 data.
Knowledge check
Answer 5 questions — 4 correct passes and earns 50 points.
1. CJC-1295 and ipamorelin act on which receptor systems respectively?
2. When do the largest natural GH pulses occur?
3. Why does eating shortly before dosing blunt a secretagogue response?
4. The core unanswered safety question specific to CJC-1295 WITH DAC is:
5. Which marker do trials use to track GH-axis activation?
Points are credited once per module, up to 5 point-earning completions per calendar month. Back to all modules