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ABSTRACT: We previously showed that a significant number of failing pregnancies are associated with production of human chorionic gonadotropin (hCG) having relatively low bioactivity. The present study was designed to compare the secretion of intact, immunoreactive hCG to the secretion of bioactive hCG during trophoblast differentiation, and to test the hypothesis that the lower bioactive: immunoreactive hCG ratios in failing pregnancies are related to reduced or impaired trophoblast differentiation. Cytotrophoblast cells were isolated from term placentas and cultured under conditions that induced or did not induce syncytiotrophoblast formation. Culture media were collected at regular intervals up to 72 h and levels of immunoreactive and bioactive hCG were measured. The differentiation of cytotrophoblast cells to multinucleated syncytiotrophoblast was monitored by immunocytochemistry and electron microscopy. During the 72 h culture period, concentrations of immunoreactive and bioactive hCG increased in both differentiating and non-differentiating cells. However, the concentrations of immunoreactive and bioactive hCG were higher under culture conditions that promoted trophoblast differentiation. Furthermore, the ratio of bioactive hCG to immunoreactive hCG was higher in differentiating cultures. When differentiation was inhibited by dimethyl sulfoxide, the secretion of bioactive hCG was reduced and the bioactive: immunoreactive hCG ratio did not change. These findings are consistent with the idea that production of bioactive hCG accompanies syncytiotrophoblast formation.
Early pregnancy: biology and medicine: the official journal of the Society for the Investigation of Early Pregnancy 01/1998; 3(4):291-300.
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ABSTRACT: There are potential interactions between various human chorionic gonadotropin (hCG) isoforms at the level of luteinizing hormone/chorionic gonadotropin (LH/CG) receptor. The objective of this study was to characterize the receptor-binding activities of the primary peptide variants of hCG including intact hCG, free beta subunit, beta-core fragment and nicked hCG, and to test the effects of these hCG variants on the binding of intact hCG. A radio-receptor assay based on cell membranes expressing recombinant human LH/CG receptors was validated and used in this study to avoid species differences in the receptor-binding specificity. The results showed that none of the hCG variants that we studied had sufficient binding affinity to compete with binding of intact hCG, nor were they able to antagonize the binding of intact hCG. These results suggest that hCG variants with either abbreviated polypeptide structures or incomplete peptide linkage are products or metabolites which do not have the tropic biological activity of the whole hormone, the intact heterodimeric hCG.
Early pregnancy: biology and medicine: the official journal of the Society for the Investigation of Early Pregnancy 10/1997; 3(3):204-12.
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ABSTRACT: In this study circulating human chorionic gonadotropin (hCG) levels in the peri-implantation period of natural cycles of normal women were characterized. The hypothesis that the bioactivity of hCG in abnormal pregnancies is different from that in normal pregnancies was tested daily through serum hCG measurements in two immunoenzymometric assays, a radioreceptor assay and a human luteinizing hormone/human chorionic gonadotropin--cyclic adenosine monophosphate--luciferase bioassay. In normal pregnancies, the levels of immunoreactive and bioactive hCG were higher than in abnormal pregnancies (p < 0.05). In addition, the slopes of the rise in concentration of hCG as measured in all four assays were significantly greater for normal pregnancies than for abnormal pregnancies (p < 0.01). The rate of rise of hCG bioactivity was significantly greater than the rise of immunoreactivity or receptor-binding activity in normal pregnancies, but this difference was not observed in abnormal pregnancies. These results indicate that: (1) A steep rise of bioactive hCG is a consistent feature of the peri-implantation period of normal pregnancies. (2) Abnormal pregnancies had a deficiency in the production of hCG, which was reflected in both the hCG levels and the rate of increase, even in the first week of implantation. (3) Some abnormal pregnancies produced hCG with lower biological activity than the hCG of normal pregnancies.
Early pregnancy: biology and medicine: the official journal of the Society for the Investigation of Early Pregnancy 09/1997; 3(3):213-24.
