Disease relevance of CRHBP

• However, in pregnancies complicated by pre-term labour (n = 9) and pre-eclampsia (n = 7), plasma CRHBP levels were significantly reduced (P < 0.01) [1].
• Furthermore, CRF-BP may represent a novel and functionally selective target for the symptomatic treatment of excessive weight gain associated with obesity of multiple etiology [2].
• Women with preterm labor show high CRF and low CRF-BP levels, supporting an involvement of this pathway in mechanism of parturition [3].
• In patients with endometriosis, no significant differences in peritoneal fluid CRF or CRF-BP levels were recorded, although in patients with stage 2 and stage 3 of the disease peritoneal fluid CRF-BP levels were higher than in healthy patients or in those with a lower grade of the disease [4].
• Compared with that in normal subjects, CRH-BP binding decreased in patients with Cushing's syndrome of pituitary or adrenal origin and in patients who were treated with a high dose of glucocorticoids over a long period of time [5].

Psychiatry related information on CRHBP

• These results raise the possibility that men with decreased amygdala CRF-BP may be more vulnerable to the effects of stress exposure on the etiology or maintenance of bipolar disorder or schizophrenia [6].

High impact information on CRHBP

• High affinity to the CRF-binding protein was prevented by introduction of glutamic acid in the binding site of the ligand [7].
• The amino acid residues Arg-23 and Arg-36 of CRFBP were identified as the sites of photoincorporation of monofunctional and bifunctional photoprobes designed on the basis of the amino acid sequence of human/rat CRF(6-33) [8].
• Nicotine abstinent subjects, but not nicotine-naive controls, experienced a 35% appetite suppression and a 25% weight gain reduction following acute and chronic administration, respectively, of CRF-BP ligand inhibitor [2].
• In marked contrast to the effects of a CRF-receptor agonist, the CRF-BP ligand inhibitor did not stimulate adrenocorticotropic hormone secretion or elevate heart rate and blood pressure [2].
• Overall, the central distribution of CRF receptor mRNA expression is similar to, though more expansive than, that of regions reported to bind CRF, and it shows limited overlap with loci expressing CRF-binding protein [9].

Chemical compound and disease context of CRHBP

• There was a good negative correlation between the levels of plasma cortisol and CRH-BP binding in patients with Cushing's syndrome before and after surgery [5].

Biological context of CRHBP

• Mapping the human corticotropin releasing hormone binding protein gene (CRHBP) to the long arm of chromosome 5 (5q11.2-q13.3) [10].
• In eight pregnancies complicated by diabetes, CRHBP levels at each gestational age were similar to those recorded for normal pregnancy [1].
• CRHBP levels returned to normal non-pregnant levels within 48 h of parturition suggesting a role for the fetoplacental unit in CRHBP production [1].
• The median plasma level of CRHBP at week 16 of normal pregnancy was 21.59 nmol/l, levels rose slightly during the early part of the third trimester (26.76 nmol/l at week 30, (P < 0.01) and fell markedly towards term (19.72 nmol/l, P < 0.01) with only 8.70 nmol/l at labour [1].
• Neurobiology of corticotropin releasing factor (CRF) receptors and CRF-binding protein: implications for the treatment of CNS disorders [11].

Anatomical context of CRHBP

• The absence of CRF-BP gene transcript in human ovarian follicles was confirmed by reverse transcription-PCR, indicating that the IrCRF-BP detected is not derived from the ovarian transcript and suggesting that the presence of IrCRF-BP and luman of capillary vessels in the thecal compartment originates from the peripheral circulation [12].
• Decreased amygdala CRF-binding protein mRNA in post-mortem tissue from male but not female bipolar and schizophrenic subjects [6].
• Novel findings are also presented on the expression of CRH-BP in the myometrium [13].
• The most pronounced down-regulation of CRH-BP and CRH-R2 occurred in laboring cervix, irrespective the length of gestation [14].
• CRF-BP was measurable in all specimens of amniotic fluid, but at 37 weeks of pregnancy the concentration in amniotic fluid was lower (10-fold) than that in maternal plasma (P < 0.01) [15].

Associations of CRHBP with chemical compounds

• A human plasma CRH-binding protein (CRH-BP) was identified and characterized by chemical cross-linking of 125I-Tyr-hCRH to human plasma using disuccinimidyl suberate [16].
• These results indicate that the CRF-BP is a glycoprotein that contains asparagine N-linked-type oligosaccharides, and such oligosaccharide chains are important for CRF-BP binding [17].
• In hypothalamic GT1-7 cells, Western blotting demonstrated rapid induction of endogenous CRH-BP expression by estradiol-bound ER, which was inhibited by TNFalpha [18].
• Levels of total, bound, and free CRH, CRH-binding protein (CRH-BP), and cortisol were measured prospectively in a large sample of pregnant Danish women who delivered preterm and term infants [19].
• Dexamethasone treatment lowered CRH-BP in all subjects (129 +/- 8 vs. 111 +/- 9; P < 0.003) [20].

Physical interactions of CRHBP

• CRF-BP binds human/rat CRF and urotensin-I with high affinity, sauvagine with moderate affinity, and ovine (o) CRF with low affinity [21].
• Three ERE half-sites in the CRH-BP promoter bound ERalpha and ERbeta in an EMSA, and disruption of ERE half-sites by site-directed mutagenesis abolished ligand-independent induction by ERalpha and ERbeta and promoter enhancement by estradiol-activated ERalpha [18].

Regulatory relationships of CRHBP

• In addition, CRH-BP inhibited CRH-induced ACTH secretion from cultured rat anterior pituitary cells [16].

Other interactions of CRHBP

• CRF-BP has differential affinities for CRF receptor antagonists, binding alpha-helical CRF-(9-41) with high affinity and [D-Phe12, Nle21,38]hCRF-(12-41) with low affinity [21].
• The inhibitory effect of the CRF-binding protein on human urocortin can be blocked by biologically inactive CRF fragments, such as CRF(9-33) [22].
• No effect was observed under the same conditions on ACTH release induced by ovine (o) CRH, which does not bind to CRH-BP [23].
• Estrogen receptor (ER)-mediated transcriptional regulation of the human corticotropin-releasing hormone-binding protein promoter: differential effects of ERalpha and ERbeta [18].
• However, using a semiquantitative PCR approach coamplifying the house-keeping gene GAPDH we detected a reduced expression of CRF-BP mRNA in ACTH-secreting pituitary adenomas when compared with normal pituitaries [24].

Analytical, diagnostic and therapeutic context of CRHBP

• The capacity of maternal and fetal plasma to bind 125I-CRH decreased at term in agreement with the quantitation of plasma CRHBP by radioimmunoassay [25].
• The hCRF-BP ELISA has a sensitivity of 2.7 fmol and a range of detection from 2.7-8000 fmol [26].
• The plasma hCRF-BP level was 0.9 +/- 0.08 nmol/L in normal human volunteers (10 men and 9 women; mean +/- SD age, 74.2 +/- 7.7 yr), decreased to 60% of basal levels 15 min after a bolus injection of 1 microgram/kg synthetic hCRF, and gradually returned to preinjection levels after 120 min [26].
• The localisation and mRNA expression of CRH, CRH receptors, and CRH-BP were studied by immunohistochemistry and reverse transcription (RT)-PCR [13].
• The binding of CRF-BP to CRF decreased after treatment with endoglycosidase H [17].

References