The biochemical properties of urinary human chorionic gonadotropin from the patients with trophoblastic diseases

Abstract

Human chorionic gonadotropin (hCG) was extracted and purified from urine of normal pregnant women and patients with hydatidiform mole and choriocarcinoma using the sam methods. Both hCG-hydatidiform mole and hCG-choriocarcinoma as well as hCG-normal pregnancy was separated into alpha and beta subunits by SDS disc electrophoresis upon treatment with 2-mercaptoethanol and showed the same immunoreactivities against anti-hCG, -alpha hCG, and -beta hCG as hCG in each radioimmunoassay. In vivo bioassay, bioactivities of hCG- normal pregnancy and hCG-hydatidiform mole were approximately 7,000 IU/mg (2nd IS), while that of hCG--choriocarcinoma was only 400 IU/mg. Conversely, the receptor binding activities in vitro of hCG-chorio carcinoma was about 3 times more effective than the other 2. Although the amino acid composition of these hCG preparations were practically identical, a great difference in the carbohydrate composition was observed. The significant difference was that while sialic acid was undetectable in hCG-choriocarcinoma approximately 8.5% of sialic acid was found in hCG-normal pregnancy and hCG-hydatidiform mole. A parallel finding was that iodinated hCG-choriocarcinoma was taken up in large quantities by the liver in comparison to the ovary which differed from that observed with hCG-normal pregnancy and hCG-hydatidiform mole in Parlow rats. The present findings support the thesis that neoplastic or malignant transformation of trophoblasts may result in an alteration of the glycosylation process, especially the sialylation, in the biosynthesis of hCG rather than the translation steps.

Between-Method Variation in Human Chorionic Gonadotropin Test Results

“…The sialic acid content and charge of hCG vary in normal and abnormal pregnancies (5)(6)(7). A hyperglycosylated form of hCG, with additional antennae on the Nand O-linked oligosaccharide side chains, is the predominant form of hCG produced in early pregnancy, around the time of implantation and in the 3 weeks that follow (8 -11 ).…”

“…Hyperglycosylated hCG can vary greatly in sialic acid content, with molecules having between 0 and 19 residues (5-7 ). The variation in sialic acid is the cause of charge variation (6,7 ). Hyperglycosylated hCG is generally more deficient in this acidic sugar than is regular hCG (5 ).…”

Characterization of a carboxyterminal peptide fragment of the human choriogonadotropin beta-subunit excreted in the urine of a woman with choriocarcinoma.

“…1, top (Fig. 1, middle panel), but also in fractions [42][43][44][45][46][47][48][49][50][51][52][53][54][55][56] corresponding to an apparent molecular size far less than that of hCG# or even hCGa. The material in fractions 42-56 was not free hCGC, since it exhibited no hCG/3 conformational immunoreactivity (SB6) (Fig.…”

“…Studies of choriocarcinoma cell lines cultured in vitro have provided evidence that the secreted forms of hCG can vary considerably in their degree of sialylation (42). Indeed, a patient with choriocarcinoma has been reported whose urinary hCG contained no measurable sialic acid (43). The extent to which peripheral desialylation of forms of hCG secreted by choriocarcinoma contributes to heterogeneity in the sialic acid content of plasma and urinary forms remains unknown.…”

Standardization of Assays for Human Chorionic Gonadotropin

“…Different recognition of variants is also a more serious problem in cancer than in pregnancy. Trophoblastic tumors produce mainly hCG, but high-risk tumors often produce an excess of hCG␤ (15,16 ) and aberrantly glycosylated hCG (17,18 ). Failure to detect these forms may explain the 58-fold differences among assays observed in an earlier study (4 ).…”