Corticotropin releasing factor receptors: characterization and actions in the anterior pituitary gland.

Abstract

Corticotropin releasing factor (CRF), which was isolated from hypothalamic extracts and sequenced in 1981, has been shown to participate in visceral and behavioral responses to stress, as well as the control of ACTH secretion (1,2). The initial event in the action of CRF in the pituitary gland is its binding to specific plasma membrane receptors, which trigger the formation of intracellular messengers responsible for the activation of ACTH release. Such receptors were first identified in rat pituitary membranes by binding studies with radioiodinated CRF (3), and were subsequently analyzed by radioassays in membranes (4) and by autoradiographic (5–8) and cytochemical techniques using biotinylated or fluorescein-conjugated CRF analogues (9,10). The use of autoradiography permitted the identification and characterization of CRF receptors in the central and peripheral nervous systems, and has greatly aided our understanding of the physiological actions of CRF in these tissues. The most common ligand used for CRF receptor studies is the radioiodinated ovine CRF derivative, Tyr-oCRF; similar receptor properties have been described using radioiodinated [NLeu21, Tyr32]oCRF (5). Analogues of rat/human CRF have given tracers with reduced biological action and lower binding activity due to peptide damage during the iodination procedure. Since ovine and human CRF bind to the CRF receptor in different species with equal affinities, oCRF can be used for studies in both rat and primates.