Corticotropin-Releasing Factor-Binding Protein: Origins and Possible Functions

Abstract

Corticotropin-releasing hormone-binding protein (CRFBP) is a 37-kD protein of 322 amino acids, containing one putative N-glycosylation site and 11 cysteines, 10 of which remain in the mature molecule (298 amino acids) and result essential for the action. CRFBP protein gene has been cloned and mapped to the distal region of chromosome 13 and loci5q in the mouse and human genomes. CRFBP is the only example of a neuropeptide-binding protein. It is produced in human and rat brain, and in human liver and placenta. In brain, the central distribution of CRFBP shares some regional overlap with CRF receptor-binding sites. Additionally, in hypothalamic and limbic structures, CRFBP has been identified in association with CRF-expressing cell groups. CRFBP has been also demonstrated in the human placenta and related membranes. Indeed, amniotic epithelium, chorionic cytotrophoblast, and maternal decidua also show intense positive CRFBP mRNA signals. Circulating CRFBP levels in healthy nonpregnant individuals show the same range values as in maternal plasma collected during the first and second trimesters of pregnancy. A rise in CRFBP levels at 30-35 weeks of pregnancy with a dramatic decrease at 38-40 weeks have been shown. At postpartum, CRFBP levels in maternal plasma reach the nonpregnant concentrations. Recombinant and native CRFBP neutralize the ACTH-releasing activity of human CRF in cultured pituitary or placental cells and, additionally, may block the activity of CRF on human pregnant endometrium prostaglandin release and on human myometrium contractility in vitro. These findings suggest that CRFBP may play a role in modulating the functions of CRF in human pregnancy.

Molecular and genetic substrates linking stress and addiction

“…Distribution of CRFR2 receptors in the brain is more restricted than CRFR1, with the highest density in the olfactory bulb, lateral septum, BNST, ventral hippocampus, and the amygdala (Van Pett et al, 2000). Along with binding to CRFR1 and CRFR2 receptors, CRF also binds to CRF-binding protein (CRF-BP), which sequesters CRF and prevents it from binding to receptors and thus activating downstream signaling cascades (Petraglia et al, 1996). …”

Detection of Specific Protein Bands with Melatonin‐Like Immunoreactivity in Different Cell Lines and Human Brain Regions

“…However, the concentration of free GHBP in the serum of mice is not regulated by GH (28). Thecorticotropin-releasing factor (CRF)± binding protein (CRFBP), which is a 37-kDa protein, is the only example of a neuropeptide-binding protein (29). In brain, the central distribution of CRFBP shares some regional overlap with CRF receptor-binding sites, suggesting that CRFBP may modulate the biological activity of corticotropin-releasing hormone (30).…”

Fetal-Placental and Decidual-Placental Units: Role of Endocrine and Paracrine Regulations in Parturition

“…A 37-kD CRH-binding protein neutralizes the ACTH-releasing activity of CRH on pituitary and placental cells, and is also able to block the prostaglandin-releasing activity of CRH on decidua and on myometrial contractility [29,30]. Thus, the decrease in CRH-binding protein concentrations in maternal and funicular plasma at the end of pregnancy, when parturition occurs at term and also prematurely, might explain the increase in CRH activity [31].…”