Corticotropin-releasing hormone-binding protein: biochemistry and function from fishes to mammals

J Endocrinol. 2002 Oct;175(1):89-97. doi: 10.1677/joe.0.1750089.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Adrenal Cortex / metabolism
  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Carrier Proteins / genetics*
  • Carrier Proteins / physiology
  • Corticotropin-Releasing Hormone / metabolism
  • Fishes / metabolism*
  • Humans
  • Mammals / metabolism*
  • Mice
  • Molecular Sequence Data
  • Pituitary Gland / metabolism*
  • Rats
  • Receptors, Corticotropin-Releasing Hormone / metabolism
  • Sequence Homology
  • Sheep
  • Thyroid Gland / metabolism
  • Xenopus


  • Carrier Proteins
  • Receptors, Corticotropin-Releasing Hormone
  • corticotropin releasing factor-binding protein
  • Corticotropin-Releasing Hormone