Corticotropin-releasing hormone-binding protein and stress: from invertebrates to humans

• Published in: Stress (Amsterdam, Netherlands) Vol. 20; no. 5; pp. 449 - 464
• Main Authors: Ketchesin, Kyle D., Stinnett, Gwen S., Seasholtz, Audrey F.
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 03.09.2017
• Subjects: Animals; Bees; Carrier Proteins - genetics; Carrier Proteins - metabolism; Copepoda; corticotropin-releasing factor; Corticotropin-releasing hormone; Corticotropin-Releasing Hormone - metabolism; CRH receptors; CRH-binding protein; Fishes; glucocorticoids; Humans; Hypothalamo-Hypophyseal System - metabolism; Invertebrates; Mice; Pituitary-Adrenal System - metabolism; Receptors, Corticotropin-Releasing Hormone - genetics; Receptors, Corticotropin-Releasing Hormone - metabolism; stress; Stress, Psychological - metabolism; corticotropin-releasing factor; stress; glucocorticoids; CRH receptors; Corticotropin-releasing hormone; CRH-binding protein
• ISSN: 1025-3890; 1607-8888
• DOI: 10.1080/10253890.2017.1322575

Corticotropin-releasing hormone (CRH) is a key regulator of the stress response. This peptide controls the hypothalamic-pituitary-adrenal (HPA) axis as well as a variety of behavioral and autonomic stress responses via the two CRH receptors, CRH-R1 and CRH-R2. The CRH system also includes an evolutionarily conserved CRH-binding protein (CRH-BP), a secreted glycoprotein that binds CRH with subnanomolar affinity to modulate CRH receptor activity. In this review, we discuss the current literature on CRH-BP and stress across multiple species, from insects to humans. We describe the regulation of CRH-BP in response to stress, as well as genetic mouse models that have been utilized to elucidate the in vivo role(s) of CRH-BP in modulating the stress response. Finally, the role of CRH-BP in the human stress response is examined, including single nucleotide polymorphisms in the human CRHBP gene that are associated with stress-related affective disorders and addiction. Lay summary The stress response is controlled by corticotropin-releasing hormone (CRH), acting via CRH receptors. However, the CRH system also includes a unique CRH-binding protein (CRH-BP) that binds CRH with an affinity greater than the CRH receptors. In this review, we discuss the role of this highly conserved CRH-BP in regulation of the CRH-mediated stress response from invertebrates to humans.