Intest Res.  2014 Apr;12(2):96-102. 10.5217/ir.2014.12.2.96.

Corticotropin-releasing Hormone and Its Biological Diversity toward Angiogenesis

• Im E

• KMID: 2284893
• DOI: http://doi.org/10.5217/ir.2014.12.2.96

Abstract

Angiogenesis is the formation of new blood vessels from existing ones and an underlying cause of numerous human diseases, including cancer and inflammation. A large body of evidence indicates that angiogenic inhibitors have therapeutic potential in the treatment of vascular diseases. However, detrimental side effects and low efficacy hinder their use in clinical practice. Members of the corticotropin-releasing hormone (CRH) family, which comprises CRH, urocortin I-III, and CRH receptors (CRHR) 1 and 2, are broadly expressed in the brain and peripheral tissues, including the intestine and cardiovascular system. The CRH family regulates stress-related responses through the hypothalamic-pituitary-adrenal axis. Therapeutic agents that target CRH family members offer a new approach to the treatment of various gastrointestinal disorders, including irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and colorectal cancer. Since the discovery that CRHR 2 has anti-angiogenic activity during postnatal development in mice, studies have focused on the role of the CRH system in the modulation of blood vessel formation and cardiovascular function. This review will outline the basic biological functions of the CRH family members and the implications for the development of novel anti-angiogenic therapies.

Keyword

Corticotropin-releasing hormone; Angiogenesis; Urocortins

MeSH Terms

Angiogenesis Inhibitors
Animals
Axis, Cervical Vertebra
Biodiversity*
Blood Vessels
Brain
Cardiovascular System
Colorectal Neoplasms
Corticotropin-Releasing Hormone*
Humans
Inflammation
Inflammatory Bowel Diseases
Intestines
Irritable Bowel Syndrome
Mice
Receptors, Corticotropin-Releasing Hormone
Urocortins
Vascular Diseases
Angiogenesis Inhibitors
Corticotropin-Releasing Hormone
Receptors, Corticotropin-Releasing Hormone
Urocortins

Figure

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  Fig. 1 Overview of the corticotropin-releasing hormone (CRH) system. The CRH system is composed of natural ligands (CRH and urocortin [Ucn] I-III), receptors (CRHR1 and 2), and binding proteins (CRH-BP and sCRHR2α). CRH and Ucn I preferentially bind to CRHR1, whereas Ucn II and Ucn III exclusively bind to CRHR2. CRH-BP and sCRHR2α bind to CRH and Ucn I to modulate the biological activities of the ligands. Human CRH (protein data bank [PDB] entry 3EHU);50 Ucn I (PDB entry 2RMF);51 Ucn II (PDB entry 2RMG);51 Ucn III (PDB entry 2RMH).51

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  Fig. 2 Functional diversity of the corticotropin-releasing hormone (CRH) system in relation to angiogenesis. The CRH system has been implicated in various biological functions pertinent to the cardiovascular system, including angiogenesis, vasodilation, alteration of blood pressure, and cardioprotection.

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