Source comparison
Receptor Pharmacology: GHRHR vs GHS-R1a
GHRHR (CJC-1295 target): Gαs-coupled, expressed exclusively in anterior pituitary somatotrophs and hypothalamic SRIF neurones. Upon GHRH/CJC-1295 binding: Gαs → adenylyl cyclase → cAMP↑ → PKA → CREB phosphorylation → GH gene transcription + immediate secretory
This comparison does not assign a generated winner or score.
- GHRHR (CJC-1295 target): Gαs-coupled, expressed exclusively in anterior pituitary somatotrophs and hypothalamic SRIF neurones. Upon GHRH/CJC-1295 binding: Gαs → adenylyl cyclase → cAMP↑ → PKA → CREB phosphorylation → GH gene transcription + immediate secretory vesicle exocytosis. EC₅₀ of CJC-1295 non-DAC at GHRHR ~0.5nM (Ki by displacement radioligand binding). Downstream: GH → liver IGF-1 (the primary anabolic mediator) → STAT5b-mediated gene transcription in muscle, bone, fat, liver. GHRHR is pituitary-restricted — no significant extra-pituitary GHRHR-mediated pharmacology.
- GHS-R1a (Ipamorelin target): Gαq-coupled, expressed in anterior pituitary somatotrophs AND hypothalamic arcuate GHRH neurones, heart (GHS-R1a cardiac actions), hippocampus (GHS-R1a-ghrelin cognitive effects), and multiple peripheral tissues. Upon ghrelin/Ipamorelin binding: Gαq → PLC → IP3 → ER Ca²⁺ release → calmodulin → somatotroph depolarisation and GH exocytosis. At the hypothalamic GHRH neurone: GHS-R1a activation increases GHRH release → additional pituitary GHRHR stimulation (central amplification). Ki of Ipamorelin at GHS-R1a ~1.0-1.5nM (selective: minimal activity at GHRHR, GnRH-R, motilin-R, GHS-R1b).
- The critical selectivity difference: Ipamorelin is among the cleanest GHS-R1a agonists in the research portfolio — it does not significantly activate cortisol (ACTH) or prolactin pathways (unlike GHRP-2 and GHRP-6 which produce ACTH +1.8-3.0-fold and prolactin +1.4-1.8-fold through shared GHRP receptor pharmacology). CJC-1295 does not activate GHS-R1a and produces negligible cortisol/prolactin stimulation. Both are therefore the preferred GH research tools when selectivity for the GH axis is required without neuroendocrine side-effect confounds.