CORTICOTROPIN-RELEASING FACTOR RECEPTORS - AN OVERVIEW

Corticotropin-releasing factor (CRF) is the primary physiological regu lator of basal and stress-induced release of ACTH, beta-endorphin and other POMC-derived peptides from the pituitary and plays a major role in the brain and periphery in coordinating endocrine, electrophysiolog ical, autonomic, behavioral and immune responses to stress. In additio n, recent clinical data implicate CRF in the etiology and pathophysiol ogy in a variety of endocrine, psychiatric and neurodegenerative disor ders. The various effects of CRF are mediated by two distinct CRF rece ptors expressed at high levels in selected brain areas, but also at di fferent levels in several other non-neuronal tissues. This chapter pro vides an overview of the current knowledge about CRF receptors includi ng tissue specificity and regulatory aspects as well as molecularbiolo gical, biochemical and pharmacological characteristics. In addition, n euroimmune, neuroendocrine and behavioral-related implications of the CRF receptor as well as its involvement in a variety of disorders are discussed. This review summarizes four decades of research beginning w ith the search for the factor that governs the release of ACTH and get ting to the recent findings including the successful cloning of differ ent receptor subtypes and the discovery of a new endogenous CRF-relate d ligand.