Corticotropin-releasing hormone (CRH) family

Corticotropin-releasing hormone and urocortins (Ucn 1, 2, and 3) are peptides which can activate G protein-coupled CRH receptors CRF1 (CRHR1) and/or CRF2 (CRHR2).

CRH is a 41-amino acid peptide, and the major regulator of adrenocorticotrophic hormone (ACTH) secretion from the anterior pituitary. In addition to hypothalamus, CRH is synthesized also in peripheral tissues, and in T lymphocytes. CHR binds to both CRF1 and CRF2.

Human urocortin 1 is a 40-amino acid peptide, which is produced in the brain, heart, and gastrointestinal organs. Ucn 1 can bind to both CRF1 and CRF2 with similar affinity.

Human urocortin 2 (stresscopin-related peptide) is a 38-43-amino acid peptide. Ucn 2 is produced in many tissues, including the brain, oesophagus, heart, and skin. Ucn 2 binds selectively CRF2.

Human urocortin 3 (stresscopin) is a 38-40-amino acid peptide. Ucn 3 is produced in many tissues, including the brain, pancreas, and intestinal epithelium. Ucn 3 binds selectively CRF2.


CRH receptor 1 is expressed in central and peripheral nervous system. In the pituitary, CRF1 activation causes the release of ACTH and β-endorphins.

CRF1 is overexpressed in pituitary adenomas. ACTH-dependent Cushing's disease accounts for 75% cases of the endogenous Cushing's syndrome. The size of lesion is usually too small to be seen using MRI. [68Ga]Ga-DOTA-CRH PET can be used to detect ACTH-dependent microadenomas (Shukla et al., 2021; Walia et al., 2021).

See also:


Kastin AJ (ed.): Handbook of Biologically Active Peptides, 2nd ed., Academic Press, 2013. eISBN: 9780123850966.


Updated at: 2022-01-27
Created at: 2022-01-27
Written by: Vesa Oikonen