Disease relevance of Crhbp

• It has previously been demonstrated that oCRF and the CRF binding protein inhibitor CRF (6-33) reduce body-weight gain in obese Zucker rats [1].
• Altogether, the present results demonstrate that food deprivation and, to a lesser extent, obesity can selectively affect the expression of CRH-BP [2].

Psychiatry related information on Crhbp

• Moreover, the magnitude of in vivo efficacy of the CRF-BP ligand inhibitor peptide in producing a mild increase in motor activity was dissociated from that of a postsynaptic CRF receptor agonist that exerted robust and long-lasting activity increases [3].
• The enhanced CRH-BP expression in the MPOA and BLA in response to food deprivation was reversed by refeeding [2].

High impact information on Crhbp

• Expression in the hypothalamus appears largely limited to the ventral premammillary and dorsomedial nuclei; only isolated CRF-BP-stained cells are apparent in neurosecretory cell groups [4].
• Thus, CRF-BP could serve to modify the actions of CRF by intra- and intercellular mechanisms, in CRF-related pathways in the central nervous system and pituitary [4].
• In recent studies to clone and characterize genes coding for the corticotropin-releasing factor-binding protein (CRF-BP), analysis of the tissue distribution of the CRF-BP gene indicated a high level of expression in the rat brain [4].
• Results from both approaches converged to indicate that CRF-BP is expressed predominantly in the cerebral cortex, including all major archi-, paleo-, and neocortical fields [4].
• Coordinate and divergent regulation of corticotropin-releasing factor (CRF) and CRF-binding protein expression in an immortalized amygdalar neuronal cell line [5].

Biological context of Crhbp

• The effects of acute stress on the regulation of central and basolateral amygdala CRF-binding protein gene expression [6].
• These data also suggest that dexamethasone may decrease the biological availability of CRF in the amygdala by increasing the expression of CRF-BP, rather than by decreasing CRF expression [5].
• These data also suggest that increased CRH-BP levels, in response to stress, may modulate the endocrine stress response by providing an additional feedback mechanism to maintain homeostasis of the hypothalamus-pituitary-adrenal axis [7].
• To better study the regulation of CRF and CRF-BP, primary amygdalar cultures were immortalized by transfection with the SV 40 large T antigen [5].
• To determine whether these changes in steady-state CRH-BP mRNA levels are caused by altered transcription or RNA stability, heteronuclear (hn) CRH-BP species were examined using ribonuclease protection assays [8].

Anatomical context of Crhbp

• Transcriptional regulation of corticotropin-releasing hormone-binding protein gene expression in astrocyte cultures [8].
• These results demonstrate that the synthesis of CRF and CRF-BP in this clonal cell line may be regulated in parallel by some agents but not by others [5].
• In anterior pituitary, CRF-BP immunoreactivity (ir) was detected in corticotropelike cells, with reaction product associated principally with secondary lysosomes and multivesicular bodies and not at all with secretory granules [9].
• Effects of acute and repeated restraint stress on corticotropin-releasing hormone binding protein mRNA in rat amygdala and dorsal hippocampus [10].
• Amygdala-kindled seizures increase the expression of corticotropin-releasing factor (CRF) and CRF-binding protein in GABAergic interneurons of the dentate hilus [11].

Associations of Crhbp with chemical compounds

• All of these increases in steady-state CRH-BP mRNA levels can be repressed by dexamethasone, a synthetic glucocorticoid [8].
• Effects of chronic cocaine exposure on corticotropin-releasing hormone binding protein in the central nucleus of the amygdala and bed nucleus of the stria terminalis [12].
• In addition, treatment of the astrocytes with phorbol myristate acetate, a protein kinase C activator, caused a robust increase in CRF-BP levels in the medium [13].
• Forskolin, dibutyryl cyclic AMP and 3-isobutyl-1-methylxanthine treatment resulted in a dose-dependent increase in CRF-BP levels detected in the medium from astrocytes and neurons [13].
• Steroids such as dexamethasone, corticosterone, hydrocortisone and, to a lesser extent, dehydroepiandosterone inhibited the stimulated release of CRF-BP from astrocytes [13].

Regulatory relationships of Crhbp

• A binding protein (CRF-BP) with the ability to inactivate CRF provides a novel target to modulate endogenous levels of CRF [3].

Other interactions of Crhbp

• Few studies have examined the effects of acute stress on the regulation of amygdala CRF-BP with other CRF system genes [6].
• Thus, CRF-BP ligand inhibitors appear to elicit generalized learning enhancement effects without mimicking the robust nonspecific behavioral actions of a CRF receptor agonist [3].
• To define the relationship between CRF-BP-ir cells and endogenous ligands for CRF-BP, double immunohistochemistry was performed to examine possible sites within the hypothalamus where CRF- or urocortin 1-ir fibres innervate regions that contain CRF-BP-ir cell bodies [14].

Analytical, diagnostic and therapeutic context of Crhbp

• Adrenalectomy decreases CRH-BP messenger RNA steady-state levels to 8% of control levels [7].
• One, 3, 10, 28, or 42 days post-treatment, animals were killed and adjacent brain sections through the CeA and BNST were processed for CRH-BP and CRH by in situ hybridization [12].
• CRF-BP was measured using a ligand immunoradiometric assay [13].
• Comparable reductions in both CRH and CRH-BP synthesis were further demonstrated with radioimmunoassay [15].
• The present study employed immunohistochemistry to characterise the distribution of CRF-BP-like-immunoreactive (-ir) cells and fibres in the rat hypothalamus [14].

References