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The Heterogeneity ofHuman ChorionicGonadotropin (hCG).III. The Occurrenceand Biological andImmunologicalActivities of NickedhCG* Laurence A. ColeA KardanaPatricia Andrade‐Gordon1991 год

The Heterogeneity of Human Chorionic Gonadotropin (hCG). III. The Occurrence and Biological and Immunological Activities of Nicked hCG*
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Аннотация: Nicks, or missing peptide linkages, have been found in hCG β-subunit between residues 44 and 45 and between residues 47 and 48. We examined the occurrence and biological and immunological activities of nicked hCG. As shown by sequence analysis, CR127 standard hCG is approximately 20% nicked, half at β44–45 and half at β47–48. Treatment with human leukocyte elastase increased the extent of nicking of CR127 standard hCG. The longer the incubation of CR127 standard with human leukocyte elastase (0, 2, and 21 h), the greater the extent of nicked hCG (20%, 46%, and 89%). As the extent of nicking increased, the receptor-binding ability diminished, as did the ability to stimulate progesterone production by rat corpus luteal cells in vitro (0.9, 0.74, and 0.29 μg/μg hCG, respectively). In a regression analysis, a linear relationship was indicated between the extent of nicking and receptor binding values (97% correlation) and between the extent of nicking and steroidogenic activity in vitro (99% correlation). From the intercepts of the regression lines, it was estimated that nicks reduced receptor binding by 11-fold and reduced the steroidogenic activity of hCG by 5-fold. We examined eight individual hCG preparations, three purified from pregnancy urine, three from urine from patients with hydatidiform mole, and two from urine from women with choriocarcinoma. In descending order, the eight individual hCG preparations were 100%, 100%, 85%, 76%, 42%, 41%, 0%, and 0% intact. Although no correlation was observed between the percent intact and the ability of the eight individual samples to displace 50% [125I]hCG in binding CG/LH receptor (r < 0.5), a close correlation was noted between the percent intact and the steroidogenic activity in vitro (98% correlation). This separated the effects of nicking on receptor binding and steroidogenic activities and indicated that while multiple factors influence receptor binding, only nicking suppresses the steroidogenic activity of bound hCG. We examined the recognition of nicked hCG molecules by different hCG immunoassays. The Hybritech Tandem assay measured total hCG and did not distinguish nicked and intact hCG molecules (in a regression analysis, immunoactivity vs. percent intact hCG, r < 0.5). In contrast, the immunometric assay using B109 hCG dimer-specific monoclonal antibody and anti-β-peroxidase only detected the intact component of hCG (in a regression analysis, immunoreactivity vs. percent intact hCG, 98% correlation). We used these assays together to estimate the percentage of intact hCG and to deduce the extent of nicking. In 38 parallel sets of serum and urine samples, 20 from pregnancy and 18 from patients with trophoblast disease, wide variation was detected in the percentage of intact hCG (range, 6–100%). Mean values for the percentage of intact hCG in serum and urine were 72 ± 22% and 76 ± 35%, respectively (mean ± SD; P > 0.5). The percentage of intact hCG was not significantly different in pregnancy (71 ± 26%) and trophoblast disease (77 ± 33%) samples (P > 0.3). We concluded that nicked hCG accounts, on the average, for approximately one quarter of the total hCG in serum and urine. The finding of a major hCG component with only minimal steroidogenic activity is novel and raises issues concerning the physiological or regulatory function of nicking and the medical significance of variations thereof. Also, the finding that a hCG assay using a dimer-specific monoclonal antibody only measures intact hCG calls into question the results from many assays in current use that employ this type of antibody. (Endocrinology 129: 1559–1567, 1991)
Год издания: 1991
Авторы: Laurence A. Cole, A Kardana, Patricia Andrade‐Gordon, MARY-ANN GAWINOWICZ, John C. Morris, Elizabeth R. Bergert, John F. O’Connor, Steven Birken
Издательство: Oxford University Press
Источник: Endocrinology
Ключевые слова: Hypothalamic control of reproductive hormones, Reproductive System and Pregnancy, Estrogen and related hormone effects
Другие ссылки: Endocrinology (HTML)
PubMed (HTML)