title: Corticotropin-releasing hormone-binding protein: biochemistry and function from fishes to mammals.
abstract: Corticotropin-releasing hormone (CRH) plays multiple roles in vertebrate species. In mammals, it is the major hypothalamic releasing factor for pituitary adrenocorticotropin secretion, and is a neurotransmitter or neuromodulator at other sites in the central nervous system. In non-mammalian vertebrates, CRH not only acts as a neurotransmitter and hypophysiotropin, it also acts as a potent thyrotropin-releasing factor, allowing CRH to regulate both the adrenal and thyroid axes, especially in development. The recent discovery of a family of CRH-like peptides suggests that multiple CRH-like ligands may play important roles in these functions. The biological effects of CRH and the other CRH-like ligands are mediated and modulated not only by CRH receptors, but also via a highly conserved CRH-binding protein (CRH-BP). The CRH-BP has been identified not only in mammals, but also in non-mammalian vertebrates including fishes, amphibians, and birds, suggesting that it is a phylogenetically ancient protein with extensive structural and functional conservation. In this review, we discuss the biochemical properties of the characterized CRH-BPs and the functional roles of the CRH-BP. While much of the in vitro and in vivo data to date support an 'inhibitory' role for the CRH-BP in which it binds CRH and other CRH-like ligands and prevents the activation of CRH receptors, the possibility that the CRH-BP may also exhibit diverse extra- and intracellular roles in a cell-specific fashion and at specific times in development is also discussed.
authors.affiliation: Departments of Biological Chemisty and Molecular, Cellular and Developmental Biology, The University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: A F
authors.initials: AF
authors.lastname: Seasholtz
authors.forename: R A
authors.initials: RA
authors.lastname: Valverde
authors.forename: R J
authors.initials: RJ
authors.lastname: Denver
mesh_terms: D000302:Adrenal Cortex / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D005399:Fishes / Q000378:metabolism*; D006801:Humans; D008322:Mammals / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010902:Pituitary Gland / Q000378:metabolism*; D051381:Rats; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism; D017385:Sequence Homology; D012756:Sheep; D013961:Thyroid Gland / Q000378:metabolism; D014981:Xenopus
chemical_list: D002352:Carrier Proteins; D018019:Receptors, Corticotropin-Releasing Hormone; C067133:corticotropin releasing factor-binding protein; D003346:Corticotropin-Releasing Hormone