CRH (Corticotropin-Releasing Hormone)

Hormonal / Stress Response

Also known as: Corticotropin-Releasing Hormone, CRF, Corticotropin-Releasing Factor, Corticorelin

Hypothalamic Releasing HormonesResearch phase: Endogenous hormone (well characterized)Regulatory: Endogenous peptide. Synthetic ovine CRH (corticorelin ovine triflutate) is FDA-approved as a diagnostic agent for Cushing syndrome.

Mechanism

CRH is a 41-amino-acid hormone released from the hypothalamus in response to stress. It activates the stress response by triggering ACTH release from the pituitary, which then stimulates cortisol production from the adrenal glands. CRH is the master switch of the HPA axis (hypothalamic-pituitary-adrenal axis) and plays key roles in anxiety, inflammation, and immune regulation.

Technical detail

CRH is a 41-amino-acid hypothalamic peptide that binds CRH-R1 (Gs-coupled) on anterior pituitary corticotrophs, activating adenylyl cyclase-cAMP-PKA signaling to stimulate POMC transcription, processing, and ACTH secretion. ACTH then drives adrenal cortisol synthesis via MC2R. CRH also binds CRH-R2 in peripheral tissues (cardiovascular, GI) with distinct effects. CRH-binding protein (CRH-BP) modulates free CRH bioavailability. Urocortins (UCN1-3) are related peptides with varying CRH-R1/R2 selectivity. Chronic CRH overactivation is implicated in depression and anxiety disorders.

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