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Gene Review

CRHBP  -  corticotropin releasing hormone binding...

Homo sapiens

Synonyms: CRF-BP, CRF-binding protein, CRFBP, CRH-BP, Corticotropin-releasing factor-binding protein, ...
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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


Biological context of CRHBP


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


  1. Plasma measurements of corticotrophin-releasing hormone-binding protein in normal and abnormal human pregnancy. Perkins, A.V., Eben, F., Wolfe, C.D., Schulte, H.M., Linton, E.A. J. Endocrinol. (1993) [Pubmed]
  2. Corticotropin-releasing factor-binding protein ligand inhibitor blunts excessive weight gain in genetically obese Zucker rats and rats during nicotine withdrawal. Heinrichs, S.C., Lapsansky, J., Behan, D.P., Chan, R.K., Sawchenko, P.E., Lorang, M., Ling, N., Vale, W.W., De Souza, E.B. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  3. Placental corticotropin-releasing factor. An update. Fadalti, M., Pezzani, I., Cobellis, L., Springolo, F., Petrovec, M.M., Ambrosini, G., Reis, F.M., Petraglia, F. Ann. N. Y. Acad. Sci. (2000) [Pubmed]
  4. Peritoneal fluid levels of immunoreactive corticotropin-releasing factor (CRF) and CRF-binding protein (CRF-BP) in healthy and endometriosic women. Florio, P., Busacca, M., Vignali, M., Viganò, P., Woods, R.J., Lowry, P.J., Genazzani, A.R., Luisi, S., Santuz, M., Petraglia, F. J. Endocrinol. Invest. (1998) [Pubmed]
  5. Glucocorticoids decrease a binding of corticotropin-releasing hormone-binding protein in human plasma. Suda, T., Sumitomo, T., Nakano, Y., Tozawa, F., Ushiyama, T., Demura, H. J. Clin. Endocrinol. Metab. (1990) [Pubmed]
  6. Decreased amygdala CRF-binding protein mRNA in post-mortem tissue from male but not female bipolar and schizophrenic subjects. Herringa, R.J., Roseboom, P.H., Kalin, N.H. Neuropsychopharmacology (2006) [Pubmed]
  7. Cortagine, a specific agonist of corticotropin-releasing factor receptor subtype 1, is anxiogenic and antidepressive in the mouse model. Tezval, H., Jahn, O., Todorovic, C., Sasse, A., Eckart, K., Spiess, J. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  8. The binding protein of corticotropin-releasing factor: ligand-binding site and subunit structure. Jahn, O., Eckart, K., Brauns, O., Tezval, H., Spiess, J. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  9. Distribution of corticotropin-releasing factor receptor mRNA expression in the rat brain and pituitary. Potter, E., Sutton, S., Donaldson, C., Chen, R., Perrin, M., Lewis, K., Sawchenko, P.E., Vale, W. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  10. Mapping the human corticotropin releasing hormone binding protein gene (CRHBP) to the long arm of chromosome 5 (5q11.2-q13.3). Vamvakopoulos, N.C., Sioutopoulou, T.O., Durkin, S.A., Nierman, W.C., Wasmuth, J.J., McPherson, J.D. Genomics (1995) [Pubmed]
  11. Neurobiology of corticotropin releasing factor (CRF) receptors and CRF-binding protein: implications for the treatment of CNS disorders. Behan, D.P., Grigoriadis, D.E., Lovenberg, T., Chalmers, D., Heinrichs, S., Liaw, C., De Souza, E.B. Mol. Psychiatry (1996) [Pubmed]
  12. Expression of genes encoding corticotropin-releasing factor (CRF), type 1 CRF receptor, and CRF-binding protein and localization of the gene products in the human ovary. Asakura, H., Zwain, I.H., Yen, S.S. J. Clin. Endocrinol. Metab. (1997) [Pubmed]
  13. Expression patterns of CRH, CRH receptors, and CRH binding protein in human gestational tissue at term. Wetzka, B., Sehringer, B., Schäfer, W.R., Biller, S., Hör, C., Benedek, E., Deppert, W.R., Zahradnik, H.P. Exp. Clin. Endocrinol. Diabetes (2003) [Pubmed]
  14. Corticotropin-releasing hormone, its binding protein and receptors in human cervical tissue at preterm and term labor in comparison to non-pregnant state. Klimaviciute, A., Calciolari, J., Bertucci, E., Abelin-Tornblöm, S., Stjernholm-Vladic, Y., Byström, B., Petraglia, F., Ekman-Ordeberg, G. Reprod. Biol. Endocrinol. (2006) [Pubmed]
  15. Changes in amniotic fluid immunoreactive corticotropin-releasing factor (CRF) and CRF-binding protein levels in pregnant women at term and during labor. Florio, P., Woods, R.J., Genazzani, A.R., Lowry, P.J., Petraglia, F. J. Clin. Endocrinol. Metab. (1997) [Pubmed]
  16. Characterization of corticotropin-releasing hormone binding protein in human plasma by chemical cross-linking and its binding during pregnancy. Suda, T., Iwashita, M., Tozawa, F., Ushiyama, T., Tomori, N., Sumitomo, T., Nakagami, Y., Demura, H., Shizume, K. J. Clin. Endocrinol. Metab. (1988) [Pubmed]
  17. Corticotropin-releasing factor-binding protein is a glycoprotein. Suda, T., Sumitomo, T., Tozawa, F., Ushiyama, T., Demura, H. Biochem. Biophys. Res. Commun. (1989) [Pubmed]
  18. Estrogen receptor (ER)-mediated transcriptional regulation of the human corticotropin-releasing hormone-binding protein promoter: differential effects of ERalpha and ERbeta. van de Stolpe, A., Slycke, A.J., Reinders, M.O., Zomer, A.W., Goodenough, S., Behl, C., Seasholtz, A.F., van der Saag, P.T. Mol. Endocrinol. (2004) [Pubmed]
  19. Preterm birth: associated neuroendocrine, medical, and behavioral risk factors. Erickson, K., Thorsen, P., Chrousos, G., Grigoriadis, D.E., Khongsaly, O., McGregor, J., Schulkin, J. J. Clin. Endocrinol. Metab. (2001) [Pubmed]
  20. The pathophysiology of circulating corticotropin-releasing hormone-binding protein levels in the human. Trainer, P.J., Woods, R.J., Korbonits, M., Popovic, V., Stewart, P.M., Lowry, P.J., Grossman, A.B. J. Clin. Endocrinol. Metab. (1998) [Pubmed]
  21. Ligand requirements of the human corticotropin-releasing factor-binding protein. Sutton, S.W., Behan, D.P., Lahrichi, S.L., Kaiser, R., Corrigan, A., Lowry, P., Potter, E., Perrin, M.H., Rivier, J., Vale, W.W. Endocrinology (1995) [Pubmed]
  22. Cloning and characterization of human urocortin. Donaldson, C.J., Sutton, S.W., Perrin, M.H., Corrigan, A.Z., Lewis, K.A., Rivier, J.E., Vaughan, J.M., Vale, W.W. Endocrinology (1996) [Pubmed]
  23. Corticotropin-releasing hormone (CRH)-binding protein: reduction in the adrenocorticotropin-releasing activity of placental but not hypothalamic CRH. Linton, E.A., Behan, D.P., Saphier, P.W., Lowry, P.J. J. Clin. Endocrinol. Metab. (1990) [Pubmed]
  24. Decreased expression of corticotropin-releasing factor-binding protein mRNA in ACTH-secreting pituitary adenomas. Dieterich, K.D., Lehnert, H. Exp. Clin. Endocrinol. Diabetes (2000) [Pubmed]
  25. Corticotrophin-releasing hormone-binding protein in human fetal plasma. Perkins, A.V., Wolfe, C.D., Eben, F., Soothill, P., Linton, E.A. J. Endocrinol. (1995) [Pubmed]
  26. Measurement of corticotropin-releasing factor (CRF), CRF-binding protein (CRF-BP), and CRF/CRF-BP complex in human plasma by two-site enzyme-linked immunoabsorbant assay. Behan, D.P., Khongsaly, O., Liu, X.J., Ling, N., Goland, R., Nasman, B., Olsson, T., De Souza, E.B. J. Clin. Endocrinol. Metab. (1996) [Pubmed]
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