Disease relevance of Crhbp

• Altered anxiety and weight gain in corticotropin-releasing hormone-binding protein-deficient mice [1].
• In contrast, adult male CRH-BP-deficient mice show significantly reduced body weight when compared with wild-type controls [1].

High impact information on Crhbp

• Accordingly, CRF-like peptides, which do not bind the CRF-BP with high affinity, do not potentiate NMDARs [2].
• Corticotropin-releasing factor requires CRF binding protein to potentiate NMDA receptors via CRF receptor 2 in dopamine neurons [2].
• Transgenic mice were generated that constitutively express elevated levels of CRH-BP in the anterior pituitary gland [3].
• However, CRH and vasopressin (AVP) mRNA levels in the transgenic mice are increased by 82 and 35%, respectively, to compensate for the excess CRH-BP, consistent with the idea that CRH-BP levels are important for homeostasis [3].
• Basal adrenocorticotropic hormone and corticosterone levels are unchanged in the CRH-BP-deficient mice, and the animals demonstrate a normal increase in adrenocorticotropic hormone and corticosterone after restraint stress [1].

Biological context of Crhbp

• CRH-BP mRNA levels increase significantly at proestrus, compared with metestrus in prolactin-positive cells (P < 0.0001) [4].
• Dual in situ hybridization analysis reveals that CRH-BP expression increases significantly in proopiomelanocortin-expressing cells at proestrus, compared with metestrus (P = 0.003), suggesting that CRH-BP expression is estrogen regulated in corticotropes [4].
• Normalized CRH-BP mRNA levels in female mice are 2.58 times greater at proestrus than diestrus [4].
• The human CRF-binding protein gene has been cloned and mapped to the distal region of chromosome 13 and loci 5q in the mouse and human genomes, respectively [5].
• The presence of a high affinity binding protein for CRH (CRH-BP) has been reported in mammals [6].

Anatomical context of Crhbp

• Overexpression of CRF-BP in vivo accelerated the loss of tail muscle cells during spontaneous metamorphosis [7].
• 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 [8].

Associations of Crhbp with chemical compounds

• These data suggest that estrogen positively regulates pituitary CRH-BP [4].

Physical interactions of Crhbp

• CRH-binding protein (CRH-BP) binds CRH with high affinity and inhibits CRH-mediated ACTH release from anterior pituitary corticotrope-like cells in vitro [9].

Regulatory relationships of Crhbp

• To investigate the functional significance of gonadotrope CRH-BP, we examined the molecular mechanisms underlying GnRH-regulated CRH-BP expression in alphaT3-1 gonadotrope-like cells [9].

Other interactions of Crhbp

• These results provide evidence of the first specific roles for CRF-R2 and CRF-BP in the modulation of neuronal activity and suggest that NMDARs in the VTA may be a target for both drugs of abuse and stress [2].
• In the pituitary, CRH-binding protein (CRH-BP) neutralizes the ACTH-releasing activity of CRH [4].
• Similarly, both CRH and urocortin bind to the CRH-binding protein (CRH-BP) [8].

Analytical, diagnostic and therapeutic context of Crhbp

• CRH-BP is endogenously expressed in alphaT3-1 cells, and quantitative real-time RT-PCR and ribonuclease protection assays demonstrate that GnRH induces a 3.7-fold increase in CRH-BP mRNA levels [9].
• To assess directly the CRH-BP function, we created a mouse model of CRH-BP deficiency by gene targeting [1].
• Ovariectomy reduces pituitary CRH-BP mRNA levels to 11% of sham-ovariectomy control levels, and estradiol benzoate treatment restores CRH-BP mRNA to control levels [4].
• 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 [8].

References