CORTICOTROPIN-RELEASING FACTOR-BINDING PROTEIN - ORIGINS AND POSSIBLEFUNCTIONS

Corticotropin-releasing hormone-binding protein (CRFBP) is a 37-kD pro tein 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 be en 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 neurope ptide-binding protein. It is produced in human and rat brain, and in h uman liver and placenta. In brain, the central distribution of CRFBP s hares some regional overlap with CRF receptor-binding sites. Additiona lly, in hypothalamic and limbic structures, CRFBP has been identified in association with CRF-expressing cell groups. CRFBP has been also de monstrated in the human placenta and related membranes. Indeed, amniot ic epithelium, chorionic cytotrophoblast, and maternal decidua also sh ow intense positive CRFBP mRNA signals. Circulating CRFBP levels in he althy nonpregnant individuals show the same range values as in materna l plasma collected during the first and second trimesters of pregnancy . A rise in CRFBP levels at 30-35 weeks of pregnancy with a dramatic d ecrease 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 c ultured pituitary or placental cells and, additionally, may block the activity of CRF on human pregnant endometrium prostaglandin release an d on human myometrium contractility in vitro. These findings suggest t hat CRFBP may play a role in modulating the functions of CRF in human pregnancy.