Ghrelin vs Mod GRF 1-29

Must be acylated at Ser3 (by GOAT enzyme) for GHSR-1a binding. Receptor activation in the pituitary stimulates GH release; hypothalamic action via NPY/AgRP neurons increases appetite and reduces energy expenditure.

Ghrelin is an endogenous 28-amino-acid peptide hormone produced primarily by X/A-like cells of the gastric fundus, characterized by a unique octanoyl modification at Ser3 required for GHS-R1a receptor binding; it is the endogenous ligand for the growth hormone secretagogue receptor and functions as a dual regulator of GH secretion and energy homeostasis. Ghrelin acts centrally via hypothalamic GHS-R1a receptors to potently stimulate GH release from the pituitary and to promote appetite through NPY/AgRP pathway activation, and has peripheral effects on gastric motility and insulin secretion, establishing it as a key integrator of nutritional status, GH axis activity, and energy balance. The pharmacology of GHS-R1a activation in humans is validated through macimorelin (Macrilen), an FDA-approved oral ghrelin receptor agonist; Phase 1 and Phase 2 randomized controlled trials of macimorelin demonstrated robust and reliable GH stimulation in adults, supporting FDA approval in 2017 for the diagnosis of adult GH deficiency and confirming the human physiological relevance of ghrelin receptor activation. Ghrelin itself is not therapeutically administered; it has a very short plasma half-life and the active acylated form is rapidly degraded in circulation; FDA-approved ghrelin receptor agonists require prescription and are indicated for diagnostic rather than therapeutic use, while ghrelin peptide is used exclusively as a research tool compound in neuroendocrine pharmacology studies.

Modified GHRH analog; binds GHRH receptors with improved stability to produce physiological GH pulses when combined with a GHRP

Mod-GRF 1-29 (also designated CJC-1293 without DAC, or tetrasubstituted GHRH[1-29]) is a synthetic analogue of the first 29 amino acids of growth hormone-releasing hormone, modified at four positions including substitution of norleucine at position 27 to improve proteolytic stability and extend the effective half-life of native GHRH 1-29, thereby producing more sustained pituitary GH stimulation per dose. Like endogenous GHRH, it acts through GHRH receptors on pituitary somatotrophs to stimulate cAMP-mediated GH synthesis and secretion, and is administered to mimic the hypothalamic pulse signal that drives GH release and downstream IGF-1 axis activity. Modified GHRH 1-29 analogues sharing the core amino acid substitutions of Mod-GRF 1-29, specifically [Nle27]GHRH(1-29)-NH2, have been administered to humans in controlled studies that documented sustained GH and IGF-1 axis effects with endocrine, metabolic, and immune endpoints characterized in age-advanced subjects. Mod-GRF 1-29 has not received FDA approval; the related compound sermorelin (unmodified GHRH 1-29) was previously FDA-approved for pediatric GH deficiency but was withdrawn by its manufacturer, and Mod-GRF 1-29 is an investigational compound not approved for any clinical indication. Naming note — Mod GRF 1-29 vs CJC-1295: the research compound marketplace uses several overlapping names for this compound. "Mod GRF 1-29" and "CJC-1295 without DAC" refer to the same tetrasubstituted GHRH(1-29) peptide. "CJC-1295 with DAC" (or simply "CJC-1295" in most clinical protocol contexts) is a different compound — it includes a Drug Affinity Complex (DAC) linker that enables albumin binding and produces a dramatically extended half-life (~8 days vs ~30 minutes for Mod GRF 1-29). CJC-1295 with DAC is used as an infrequent injection (weekly or biweekly) while Mod GRF 1-29 / CJC-1295 without DAC is used at each injection session, typically immediately before or alongside a GHRP such as ipamorelin to maximally leverage the GH pulse window. Dosage in research protocols: Mod GRF 1-29 is typically used at 100 mcg per injection alongside ipamorelin or another GHRP, administered 2–3 times daily or immediately before sleep to align with natural GH secretion peaks. Subcutaneous injection after reconstitution with bacteriostatic water is the standard route. Provider availability for Mod GRF 1-29 and CJC-1295 compounds is listed in the PeptideBase directory.