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 CRHlike 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 cellspecific fashion and at specific times in development is also discussed.

Chronic low dose ovine corticotropin releasing factor or urocortin II into the rostral dorsal raphe alters exploratory behavior and serotonergic gene expression in specific subregions of the dorsal raphe

“…Unfortunately, our results do not provide strong evidence to favor the role of one CRF receptor over another in their actions on serotonergic neurons and behavior described in this paper. Furthermore, CRF binding protein is present in the DRN and could modulate the availability of CRF family neuropeptides there (Potter et al, 1992, Seasholtz et al, 2002 thus altering local peptide concentrations. More specific pharmacologic and transgenic experiments should help clarify the roles of each receptor type as well as CRF-BP in the DRN.…”

“…Indeed, several studies favor the involvement of CRF 2 receptors in regulating DRN functions, especially in the more caudal regions of the DRN (Hammack et al, 2003, Staub et al, 2006. Additionally, CRF binding protein (CRF-BP) has been reported to modulate the availability of CRF family peptides (Potter et al, 1992, Seasholtz et al, 2002. oCRF and rat UCNII may have different affinities for CRF-BP.…”

Stress elevates corticotropin-releasing factor (CRF) and CRF-binding protein mRNA levels in rainbow trout (Oncorhynchus mykiss)

“…The activity of the stress axis can be modulated at several levels including pituitary changes in the expression of the CRF1 receptor or CRF-binding protein (CRF-BP). The function of CRF-BP is still unclear although studies do support an inhibitory role for CRF-BP on CRF action (Seasholtz et al 2002). Rodent CRF-BP blocks CRF-induced adrenocorticotropic hormone (ACTH) release from pituitary cells in vitro (Potter et al 1991, Cortright et al 1995.…”

“…The binding of CRF to plasma CRF-BP would prevent inappropriate stimulation of the stress axis by placental CRF (Petraglia et al 1993). CRF-BP is present in corticotropes of the anterior pituitary of rodents, implying that it could modulate the action of receptorbound CRF (Seasholtz et al 2002). In a line of transgenic mice overexpressing CRF-BP in the anterior pituitary only, it was hypothesized that the elevated hypothalamic CRF expression observed may have a role to maintain normal levels of free CRF and normal activity of the stress axis (Burrows et al 1998).…”

Mechanism(s) of in utero meconium passage

“…33 Our immunohistochemical investigation revealed expression of CRF-binding protein in the smooth muscle-enteric unit. 34 We observed a marked decrease in smooth muscle expression of CRF-binding protein and a simultaneous increase in myenteric neuronal somas at term, indicating that this protein is a critical regulator of CRF and urocortin functions at the level of smooth muscle-enteric unit in sheep fetal distal colon.…”