Mechanism of Action
GHRHR Signaling
GHRH binds GHRHR on pituitary somatotrophs, activating Gs-adenylyl cyclase-cAMP-PKA pathway. PKA phosphorylates CREB driving GH gene transcription, and activates voltage-gated calcium channels triggering GH exocytosis. GHRH acts in concert with ghrelin/" class="wiki-internal-link">ghrelin (at GHS-R1a) for maximal GH release; the two pathways are synergistic.
Physiological GH Pulsatility
GHRH pulses from the hypothalamus, timed to slow-wave sleep, drive the nocturnal GH surge. Somatostatin provides the inhibitory counterpart, creating characteristic pulsatile GH release. Sermorelin and other GHRH analogs preserve this physiological pulsatility, a key distinction from exogenous GH which suppresses endogenous axis feedback.
Research Summary
GH Deficiency (Sermorelin)
FDA ApprovedSermorelin (GHRH 1-29-NH2) is FDA-approved for GH deficiency in children. It stimulates endogenous GH production rather than replacing GH directly, preserving pituitary responsiveness. In adults, sermorelin is used off-label for age-related GH decline with clinical data showing increased IGF-1, lean mass, and improved sleep quality.
HIV Lipodystrophy (Tesamorelin)
FDA ApprovedTesamorelin is FDA-approved as Egrifta for HIV-associated lipodystrophy, reducing visceral adipose tissue by 15-20% over 26 weeks. This validated GHRH agonism for metabolic indications in adults beyond pediatric GH deficiency.
Cognitive Effects
Clinical ResearchGHRH analogs improve cognitive function in aging adults and MCI patients in randomized trials, independent of body composition changes. Verbal memory and executive function improvements have been documented, possibly via direct GHRH receptor effects in the hippocampus or downstream IGF-1 neuroprotection.
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Research Protocols
| Goal | Dose | Frequency | Route |
|---|---|---|---|
| GH deficiency treatment (sermorelin) | 0.2-0.3 mg SC at bedtime | Daily | Subcutaneous |
| HIV lipodystrophy (tesamorelin) | 2 mg SC daily | Daily | Subcutaneous |
| GH stimulation test (GHRH 1-44) | 1 ug/kg IV | Single dose | Intravenous |
GHRH and analogs are WADA prohibited. Require prescriptions. Not for athletic performance enhancement.
Interactions
Safety Profile
Sermorelin and tesamorelin have well-characterized safety profiles. Side effects include injection site reactions, water retention, and mild glucose elevation. Contraindicated in active malignancy. WADA prohibited. Long-term use may cause pituitary desensitization if administered continuously rather than pulsatilely.
References
- [1]Guillemin R, et al. Growth hormone-releasing factor from a human pancreatic tumor that caused acromegaly. Science. 1982;218(4572):585-587.
- [2]Falutz J, et al. Metabolic effects of a growth hormone-releasing factor in patients with HIV. N Engl J Med. 2007;357(23):2359-2370.
- [3]Vitiello MV, et al. Growth hormone releasing hormone improves the cognition of healthy older adults. Neurobiol Aging. 2006;27(2):318-323.