Some qualitative differences of hCG in serum from early and late pregnancies and trophoblastic diseases

Wide, Leif; Hobson, B. M.

doi:10.1530/acta.0.1160465

Cited by 35 publications

(17 citation statements)

References 11 publications

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“…The existence of hCG glycoforms has been documented for some time (Fein et al 1980, Wide & Hobson 1987, Skarulis et al 1992, Nemansky et al 1998. Most of this work was either based on isoelectric focusing patterns which are not feasible for general measurements or else by carbohydrate analysis on a few specimens.…”

Section: Discussion Hcg Isoforms In Early and Later Pregnancy Urinementioning

confidence: 99%

Differential expression of human chorionic gonadotropin (hCG) glycosylation isoforms in failing and continuing pregnancies: preliminary characterization of the hyperglycosylated hCG epitope

Kovalevskaya

Birken²,

Kakuma³

et al. 2002

Journal of Endocrinology

115

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Human chorionic gonadotropin (hCG) glycoforms change as pregnancy progresses. We have developed an antibody (B152) which can measure a hyperglycosylated early pregnancy isoform of hCG. This putative hyperglycosylated form of hCG arises very early in pregnancies and is rapidly replaced by an isoform that predominates for the remainder of the pregnancy. The profiles of these hCG glycoforms are measured as a ratio of values of two immunometric assays. The profiles of these ratios differ between pregnancies which persist and those which will experience early failure.In this report, daily urine hCG isoform ratios from donor eggs (no exogenous hCG pretreatment), in vitro fertilization pregnancies were profiled and analyzed from the first day following embryo transfer (ET). Significant differences were found between continuing pregnancy and pregnancy loss throughout days 5-20 post-ET. When hCG isoform ratios were analyzed from the first day of detectable hCG, pregnancy loss could be predicted in the case of a single fetus both during the 5-to 10-day time segment (P=0·018) and the 10-to 15-day time segment (P=0·045). When single and multiple fetus pregnancies were analyzed together significance was approached in the 10-to 15-day time period (P=0·058).In a second population of pregnant women who conceived naturally, in whom urine samples were collected at approximately weekly intervals to either term birth or clinical spontaneous abortion, the ratio could discriminate between miscarriages and normal term pregnancies (P=0·043). In later pregnancy, the ratio of hCG isoforms declined more rapidly in miscarriages than in term pregnancy.Antibody B152 was produced using a choriocarcinomaderived hCG (C5), which was hyperglycosylated at both N-and O-linked sites and was 100% nicked at position [47][48] . Western blot analyses supported the assay results showing that early pregnancy urine does not contain nicked C5-like hCG. Also, the early pregnancy hCG appeared to be the same size as later pregnancy hCG as judged by SDS gel electrophoresis. A series of Western blot analyses and immunoassays conducted with the samples either non-reduced or reduced showed that B152 is directed to a linear epitope located in the COOHterminal peptide region of the subunit. This indicated that only the O-glycan groups and not the N-linked glycans are part of the antibody epitope.

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Section: Discussion Hcg Isoforms In Early and Later Pregnancy Urinementioning

confidence: 99%

Differential expression of human chorionic gonadotropin (hCG) glycosylation isoforms in failing and continuing pregnancies: preliminary characterization of the hyperglycosylated hCG epitope

Kovalevskaya

Birken²,

Kakuma³

et al. 2002

Journal of Endocrinology

115

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“…This theory is supported by the different glycosylation patterns found on hCG 1 (8, 15, 26 -28) and on free ␣ subunit from normal pregnancy (8,26), choriocarcinoma (22)(23)(24), and non-trophoblastic neoplasms (25,29). In addition, less highly charged isoforms of hCG were found in late pregnancy (30), and further studies of its electrophoretic mobility suggested that its glycosylation patterns change during the early second trimester of pregnancy (31). Previously, we have presented lectin data that implied increased branching and higher incorporation of fucose into carbohydrate moieties in late pregnancy (32).…”

mentioning

confidence: 90%

Developmental Changes in the Glycosylation of Glycoprotein Hormone Free α Subunit during Pregnancy

Nemansky¹,

Thotakura²,

Lyons³

et al. 1998

Journal of Biological Chemistry

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Glycoprotein hormone ␣ subunit, in its free form (free ␣), is a major placental product. Its glycosylation was found to change dramatically during the advancement of pregnancy. In this study, we have analyzed these glycosylation changes in five normal pregnancies. Binding to Lens culinaris lectin increased dramatically in all subjects between weeks 14 and 17 from the last menstrual period, indicating more core fucosylation as well as possible changes in branching of glycans. Studies using Datura stramonium agglutinin confirmed that the type of triantennary branching changed in this period of pregnancy. The precise structural nature of these changes was determined by high-pH anion-exchange chromatography and electrospray ionization mass spectrometry. Amounts of core fucosylation and of triantennary glycans increased substantially from early to late second trimester, and a shift was observed from 134/ 133-toward predominantly 136/136-branched triantennary structures. The glycosylation changes occurred in all five individuals at the same time period in gestation, suggesting developmental regulation of N-acetylglucosaminyltransferases IV and V and ␣6-fucosyltransferase during normal pregnancy. These enzymatic activities also appear to be affected in malignant transformation of the trophoblast. Our findings have important implications for the proposed use of specific forms of glycosylation as markers for cancer, as the relative amounts of these glycans in normal pregnancy will be determined by gestational age.Glycoprotein hormone ␣ subunit is common to the heterodimeric hormones chorionic gonadotropin, luteinizing hormone, follicle-stimulating hormone, and thyroid-stimulating hormone. However, in its free form (free ␣ subunit), it is an important placental (1, 2) and pituitary (3) product, and it has been shown to have functions that are independent of the dimeric hormones (4 -7). Glycosylation of free ␣ differs from glycosylation of the combined form (8, 9). The combination of ␣ and ␤ for heterodimer formation takes place in the endoplasmic reticulum prior to processing of the immature glycans. In ␣ subunits that have not combined with a ␤ subunit, enzymes from the post-translational glycosylation machinery have access to substrate sites that are normally protected by the ␤ subunit of the heterodimer. As a result, the free form of ␣ subunit generally contains more elaborate oligosaccharide branching as well as higher amounts of core fucosylation than ␣ subunit obtained from dissociated hormone (8, 9). These characteristic glycosylation patterns prevent secreted free ␣ subunits from combining with ␤ subunits that might be encountered extracellularly, thus ensuring a population of free ␣ molecules (9, 10).The structural diversity of complex-type N-linked glycans is initiated by GlcNAc branching of the trimannosyl core and continues with the action of different glycosyltransferases that further extend these antennae (11). Specifically, the activity of N-acetylglucosaminyltransferase IV initiates the 134/133-branch of c...

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“…This fraction decreased to less than half (47%) late in the third trimester (Diaz-Cueto et al 1996). In contrast, Wide & Hobson (1987) found that the hCG of early pregnancy was more 'choriocarcinoma-like' by virtue of its greater biological activity than the hCG of normal pregnancy. Fein et al (1980), in a study which employed gel filtration, determined that first trimester hCG was a larger size than that of the third trimester.…”

Section: Discussionmentioning

confidence: 88%

“…They may occur as a concomitant of its origin (Wide & Hobson 1987, Birken et al 1996, or metabolic transformation (Nisula et al 1989). The most prominent differences documented to date are between the hCG produced by choriocarcinoma and that of mid-first trimester normal pregnancy, with choriocarcinoma-derived hCG having a generally higher content of more highly branched oligosaccharides (Cole 1987, Elliott et al 1997.…”

Section: Introductionmentioning

confidence: 99%

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Early pregnancy human chorionic gonadotropin (hCG) isoforms measured by an immunometric assay for choriocarcinoma-like hCG

Kovalevskaya¹,

Birken²,

Kakuma³

et al. 1999

Journal of Endocrinology

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Human chorionic gonadotropin (hCG) exhibits molecular heterogeneity in both its protein and carbohydrate moieties. This communication describes changes in hCG isoforms detected directly in clinical samples. These isoforms, quantified in blood or urine specimens, show a progression of change throughout normal pregnancy. Early pregnancy produces a type of hCG that resembles, in terms of immunoreactivity, a major form of hCG excreted in choriocarcinoma. The isoforms predominate for the first 5-6 weeks of gestation and then diminish, being replaced with the hCG isoforms which predominate throughout the remainder of pregnancy. The alteration in hCG isoform content occurs in both blood and urine. The progression of isoforms is best delineated by calculating the change in the ratio of the two forms, as many hCG assays either do not detect or fail to discriminate among these isoforms. An analogous pattern of hCG isoforms was observed in patients with in vitro fertilization pregnancies. hCG isolated from the pituitary displayed binding characteristics similar to those of the hCG derived from normal pregnancy urine. The early pregnancy hCG isoforms appear to have a differential expression in normal pregnancy as opposed to pregnancies which will not carry to term, suggesting that a determination of the relative balance of hCG isoforms may have diagnostic application in predicting pregnancy outcome.

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Some qualitative differences of hCG in serum from early and late pregnancies and trophoblastic diseases

Cited by 35 publications

References 11 publications

Differential expression of human chorionic gonadotropin (hCG) glycosylation isoforms in failing and continuing pregnancies: preliminary characterization of the hyperglycosylated hCG epitope

Differential expression of human chorionic gonadotropin (hCG) glycosylation isoforms in failing and continuing pregnancies: preliminary characterization of the hyperglycosylated hCG epitope

Developmental Changes in the Glycosylation of Glycoprotein Hormone Free α Subunit during Pregnancy

Early pregnancy human chorionic gonadotropin (hCG) isoforms measured by an immunometric assay for choriocarcinoma-like hCG

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