THE BIOLOGICAL AND CLINICAL-SIGNIFICANCE OF NICKS IN HUMAN CHORIONIC-GONADOTROPIN AND ITS FREE BETA-SUBUNIT

Citation
La. Cole et al., THE BIOLOGICAL AND CLINICAL-SIGNIFICANCE OF NICKS IN HUMAN CHORIONIC-GONADOTROPIN AND ITS FREE BETA-SUBUNIT, The Yale journal of biology & medicine, 64(6), 1991, pp. 627-637
Citations number
32
Language
INGLESE
art.tipo
Article
ISSN journal
0044-0086
Volume
64
Issue
6
Year of publication
1991
Pages
627 - 637
Database
ISI
SICI code
0044-0086(1991)64:6<627:TBACON>2.0.ZU;2-R
Abstract
Human chorionic gonadotropin (hCG) is a glycoprotein hormone composed of two dissimilar subunits, alpha and beta. Nicks or missing peptide l inkages have been found in the beta-44-52 region of the beta-subunit o f hCG, whether from pregnancy or trophoblast disease. This article rev iews recent reports about the location of nicks in hCG, their origin a nd occurrence, their effects on the steroidogenic and receptor-binding activities of hCG, and on the immunological activities of hCG and its free beta-subunit. Taken together, the reports show: (1) nicks occur primarily between beta-47 and beta-48, and to a lesser extent between beta-44 and beta-45; (2) the extent of nicking in hCG samples varies w idely, from undetectable to 100 percent of molecules; (3) nicks greatl y reduce the steroidogenic activity of hCG in vitro (nicked molecules have less than 20 percent of the activity of the intact hormone); (4) nicks may occur at the trophoblast-myometrial interface or in the circ ulation by the action of human leucocyte elastase or similar leucocyti c protease; (5) hCG testing kits using dimer-specific antibodies may n ot detect nicked molecules and may give different results from those u sing other antibodies; (6) hCG international reference preparations an d the CR series of hCG standards are variably nicked (10 percent to 20 percent), complicating the problem of discordant hCG results in nick- sensitive assays; (7) results from commonly used immunoassays for meas urement of the hCG free beta-subunit vary by as much as tenfold becaus e some of the antibodies employed do not detect nick free beta-subunit .