Mouse models of altered CRH-binding protein expression.
CRH is the key physiological mediator of the endocrine, autonomic, and behavioral responses to stress. The recent characterization of urocortin, a new mammalian CRH-like ligand, adds to the complexity of the CRH system. Both CRH and urocortin mediate their endocrine and/or synaptic effects via two classes of CRH receptors. Similarly, both CRH and urocortin bind to the CRH-binding protein (CRH-BP). This secreted binding protein is smaller than the CRH receptors, but binds CRH and urocortin with an affinity equal to or greater than that of the receptors, and blocks CRH-mediated ACTH release in vitro. Several regions of CRH-BP expression colocalize with sites of CRH synthesis or release, suggesting that this binding protein may have a profound impact on the biological activity of CRH (or urocortin). While in vitro and in vivo studies have characterized the biochemical properties and regulation of the CRH-BP, animal models of altered CRH-BP expression can provide additional information on the in vivo role of this important modulatory protein. This review focuses on three mouse models of CRH-BP overexpression or deficiency. These animal models show numerous physiological changes in the HPA axis and in energy balance, with additional alterations in anxiogenic behavior. These changes are consistent with the hypothesis that CRH-BP plays an important in vivo modulatory role by regulating levels of "free" CRH and other CRH-like peptides in the pituitary and central nervous system.
Seasholtz
A F
AF
Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA. aseashol@umich.edu
Burrows
H L
HL
Karolyi
I J
IJ
Camper
S A
SA
D000818:Animals; D001007:Anxiety / Q000503:physiopathology; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D003346:Corticotropin-Releasing Hormone / Q000737:chemistry / Q000378:metabolism*; D004435:Eating / Q000502:physiology; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics / Q000378:metabolism*; D023421:Models, Animal; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism*; D015430:Weight Gain / Q000502:physiology
D002352:Carrier Proteins; D018019:Receptors, Corticotropin-Releasing Hormone; D003346:Corticotropin-Releasing Hormone