The Molar Vesicle Fluid Contains the β-Core Fragment of Human Chorionic Gonadotropin

Khan, Sharmin; Katabuchi, H.; Araki, Masako; Ohba, Takayoshi; Okamura, Hitoshi; Nishimura, Ryuichiro

doi:10.1053/plac.1999.0453

Cited by 8 publications

(9 citation statements)

References 23 publications

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“…However, we recently reported that hCG cf was directly produced not only by placental tissue (Udagawa et al 1998) but also by cancer cells in vitro, including choriocarcinoma cell lines (Okamoto et al 2001). As for trophoblastic disease, there are limited data describing hCG cf immunoreactivity in the tissue (Kardana et al 1988, Khan et al 2000, and the present study was performed to examine the presence and Table 2). (B) Choriocarcinoma (sample no.…”

Section: Discussionmentioning

confidence: 92%

“…Little information is currently available regarding concentrations of hCG cf in the serum of patients with GTD, and to the best of our knowledge, the present study is the first to demonstrate the presence of hCG cf immunoreactivity in their serum. Khan et al (2000) failed to detect hCG cf in the serum of patients with hydatidiform mole. This discrepancy is likely to be due to the difference in the specificity of the antibody against hCG cf.…”

Section: Discussionmentioning

confidence: 94%

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Human chorionic gonadotropin (hCG) beta-core fragment is produced by degradation of hCG or free hCG beta in gestational trophoblastic tumors: a possible marker for early detection of persistent postmolar gestational trophoblastic disease

Okamoto

Matsuo²,

Niu³

et al. 2001

Journal of Endocrinology

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The present study was undertaken to investigate whether human chorionic gonadotropin (hCG) -core fragment (hCG cf) was directly produced by gestational trophoblastic tumors. Immunoreactivity of hCG cf was demonstrated in the extracts as well as in the culture media of hydatidiform mole tissues. It was also present in the extracts of choriocarcinoma tissues, and its molar concentration exceeded that of intact hCG. The presence of hCG cf was then confirmed by gel chromatography and Western blot analysis. Immunohistochemistry showed localization of hCG cf immunoreactivity to the syncytiotrophoblasts and scattered cells in the stroma of mole tissue, and to syncytiotrophoblastic cells in choriocarcinoma. Immunoreactivity of hCG cf was also detected in the sera of the patients with gestational trophoblastic disease, although the hCG cf/hCG ratio was less than one hundredth of that in the tissue extracts. Serial measurement of serum hCG cf levels after mole evacuation showed that they declined much more rapidly than those of hCG and became undetectable in the patients with subsequent spontaneous resolution, while hCG cf remained or became detectable before the rise of hCG was observed in the patients with subsequent persistent trophoblastic disease. Taken together, these results suggest that hCG cf is directly produced by gestational trophoblastic tumors, and monitoring of hCG cf in the serum after mole evacuation may be useful for early prediction of subsequent development of postmolar persistent trophoblastic disease.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 94%

Human chorionic gonadotropin (hCG) beta-core fragment is produced by degradation of hCG or free hCG beta in gestational trophoblastic tumors: a possible marker for early detection of persistent postmolar gestational trophoblastic disease

Okamoto

Matsuo²,

Niu³

et al. 2001

Journal of Endocrinology

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“…hCG cf-like material has also been reported in molar fluid, and it is hypothesized that it is derived from macrophage processing of hCG (Iles et al 1999, Khan et al 2000. It is nevertheless likely that the major source of urinary hLH cf is from circulating LH, because of the pattern of peaking of hLH cf in urine 24-48 h after the LH surge during the menstrual cycle (Iles et al 1992, Neven et al 1993, O'Connor et al 1998.…”

Section: Discussionmentioning

confidence: 99%

Metabolism of gonadotropins: comparisons of the primary structures of the human pituitary and urinary LH beta cores and the chimpanzee CG beta core demonstrate universality of core production

Birken

Gawinowicz²,

Maydelman³

et al. 2001

Journal of Endocrinology

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The gonadotropins are a family of closely related heterodimeric glycoprotein hormones homologous in structure to disulfide-knot growth factors. Metabolic proteolytic processing in vivo of this disulfide cross-linked region results in urinary excretion of a residual highly stable core structure. The primary structure of the pituitary form of the hLH core was reported earlier, but it has proved difficult to isolate the urinary core, although antibodies to the pituitary core demonstrated its presence. By conventional and immunoaffinity methods, the urinary core has been isolated and its structure determined by both chemical and mass spectrometric methods. The urinary hLH core is the same as the pituitary-extracted hLH core, 6-40 disulfide bridged to 55-93, except that the pituitary core is more heterogeneous containing also 49-93. These findings imply a dual origin of urinary cores, both directly from a secreting tissue and by kidney processing of circulating hormone. We also found that pregnant chimpanzees excrete a CG core with a primary structure identical to that of the human CG core of pregnancy. In conclusion, gonadotropin core generation and urinary excretion of nearly identical gonadotropin metabolites is common among primates. Although possible biological functions of these core fragments remain unproven, they have diagnostic utility because of their stability and abundance.

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“…Ensaios específicos imunoenzimáticos e radiomé-tricos com reação cruzada negligenciável com as outras formas variantes de hCG podem ser obtidos comercialmente para uso clínico 8,61 . O CF-hCG pode ser detectado em grandes quantidades na urina de gestantes normais, urina de mulheres não grávidas, neoplasia trofoblástica gestacional, líquido amniótico, líquido das vesículas na mola hidatiforme, líquido folicular ovariano após uso de hCG para indução da ovulação, urina de recém-nascidos, sêmen, placenta e extratos de vá-rios tecidos 10,64 . Quantidades muito pequenas podem ser detectadas no soro de gestantes ou mesmo indivíduos não gestantes 65 .…”

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“…Equivalência ou superioridade deste marcador, em relação ao teste triplo, na detecção de fetos com sín-drome de Down tem sido encontrada 74 . Além da produção renal, tecido placentário, vesículas molares ou coriocarcinoma também secretam CF-βhCG 11,64,76 . Este fragmento-núcleo da βhCG é de relevância clínica também no acompanhamento de gestantes com neoplasia trofoblás-tica ou indivíduos com câncer, seja este ginecoló-gico ou não 77 .…”

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Formas moleculares da gonadotrofina coriônica humana: características, ensaios e uso clínico

Medeiros¹,

Norman²

2006

Rev. Bras. Ginecol. Obstet.

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A gonadotrofina coriônica humana (hCG) é estruturada pela combinação não covalente de duas subunidades, alfa (αhCG) e beta (βhCG), sintetizadas separadamente pelo tecido trofoblástico normal, mola hidatiforme, coriocarcinoma, células hipofisárias e tecidos tumorais de diversos tipos histológicos. A síntese da cadeia peptídica e sua glicosilação na célula secretora envolve complexa ação de várias enzimas. Esta complexidade resulta na secreção de moléculas heterogêneas. As diferentes formas moleculares secretadas podem ser encontradas no soro, urina e líquido amniótico de gestantes; soro, urina e vesículas em pacientes com mola hidatiforme ou coriocarcinoma e em fluidos biológicos de mulheres não grávidas e homens normais ou acometidos de tumores de diferente origem embrionária. Tanto a molécula hCG nativa, intacta,como suas subunidades nas formas livres e as variantes hCG hiperglicosilada (H-hCG), hCG clivada (N-hCG) e fragmento-núcleo de βhCG (CF-βhCG) têm aplicabilidade clínica relevante. Dependendo da forma molecular mais prevalente ou da proporção da molécula variante/molécula hCG intacta numa determinada condição clínica, há indicação para a dosagem específica de uma ou mais destas moléculas. Este texto revê o conhecimento básico e analisa o uso da hCG e suas variantes na detecção precoce da gravidez ectópica ou gestantes em risco de abortamento, na identificação precoce de anomalias cromossômicas êmbrio-fetais e estima o risco da gestação de evoluir com pré-eclâmpsia ou crescimento intra-uterino restrito. Examina, ainda, fora da gravidez, o emprego destas moléculas como marcadores laboratoriais de tumores com diferentes tipos histológicos e seguimento após a terapia inicial. Conclui-se ser útil o uso da dosagem de hCG e suas moléculas variantes na prática clínica, mas a dificuldade no desenvolvimento e obtenção de ensaios mais sensíveis e específicos restringe a aplicação mais universal destes marcadores hormonais. PALAVRAS-CHAVE:Gonadotrofina coriônica; Beta hCG livre; Núcleo-fragmento de βhCG; Formas moleculares de hCG ABSTRACTThe human chorionic gonadotropin (hCG) results from a non-covalent linkage of two subunits, alpha (αhCG) and beta (βhCG), separately synthesized by normal trophoblastic tissue, hydatiform mole, choriocarcinoma, pituitary cells, and tumoral tissues of different histologic types. The peptide chain and its further glycosylation in the secretory cell involves the complex action of different enzymes. This complexity results in the secretion of heterogeneous molecular forms. The different molecules might be found in serum, urine and amniotic fluid of pregnant women; serum, urine, and vesicles of patients with hydatiform mole or choriocarcinoma and in other biological fluids of normal non-pregnant women and men or patients with different embryonary types of cancer. Both the intact hCG molecule and its free subunits and the hyperglycosylated (H-hCG), nicked (N-hCG) and core fragment of βhCG (CF-βhCG) variant forms have relevant clinical use. Depending on the prevalent molecular form or the ...

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The Molar Vesicle Fluid Contains the β-Core Fragment of Human Chorionic Gonadotropin

Cited by 8 publications

References 23 publications

Human chorionic gonadotropin (hCG) beta-core fragment is produced by degradation of hCG or free hCG beta in gestational trophoblastic tumors: a possible marker for early detection of persistent postmolar gestational trophoblastic disease

Human chorionic gonadotropin (hCG) beta-core fragment is produced by degradation of hCG or free hCG beta in gestational trophoblastic tumors: a possible marker for early detection of persistent postmolar gestational trophoblastic disease

Metabolism of gonadotropins: comparisons of the primary structures of the human pituitary and urinary LH beta cores and the chimpanzee CG beta core demonstrate universality of core production

Formas moleculares da gonadotrofina coriônica humana: características, ensaios e uso clínico

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