Detection of the Free Beta Subunit of Human Chorionic Gonadotropin (Hcg) in Cultures of Normal and Malignant Trophoblast Cells, Pregnancy Sera, and Sera of Patients With Choriocarcinoma

Cole, Laurence A.; Hartle, Richard J.; LaFerla, John J.; Ruddon, Raymond W.

doi:10.1210/endo-113-3-1176

Cited by 61 publications

(26 citation statements)

References 6 publications

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“…A variation in the ratio between ß-hCG(I) and hCG(I) activités has been shown to be caused by different amounts of free ß-hCG subunits (Vaitu¬ kaitis 1974; Reuter et al 1980;Cole et al 1983Cole et al , 1984Hay 1985;Norman et al 1985a,b). Like the other glycoproteins hormones, hCG exhibits a considerable polymorphism and in some clinical situations, forms may be secreted with a different degree of cross-reactivity in the ß-hCG or in the hCG assay system, which will also influence the ratio ß-hCG(I)/hCG(I).…”

Section: Discussionmentioning

confidence: 99%

“…However, the de¬ gree of cross-reactivity is not known. There is evidence suggesting that native free a-hCG subunits in the placenta and in the circulation are different from those dissociated from purified urinary hCG preparations (Cole et al 1983;Nishimura et al 1983;Posillico et al 1985). There is ample evidence to suggest that the form of hCG produced in early and late pregnancy and in o.ioo Relationship between concentration of hCG(I) and the ratio of ß-hCG(I) to hCG(I) in serum specimens obtained early (E) and late (L) in pregnancy, in women with gestational choriocarcinoma (C), and in men with testicular trophoblastic tumours (T).…”

Section: Discussionmentioning

confidence: 99%

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

Wide

Hobson²

1987

Acta Endocrinologica

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Twenty-four sera were obtained from women in the first and third trimester of pregnancy, women with gestational choriocarcinoma, and men with testicular hCG-producing tumours. The hCG-activity was measured by an in vivo bioassay (B) based upon the increase in mouse uterine weight. The sera were also analysed by three immunoassays (I), one for hCG, one for \g=a\-hCGsubunits, and one for \g=b\-subunits. All sera were also subjected to electrophoresis in 0.17% agarose suspension in 0.075 mol/l sodium veronal buffer at pH 8.6, and median charge, expressed as median mobility, was estimated for hCG. The metabolic clearance rate (MCR) of hCG in serum in early and late pregnancy and from one patient with choriocarcinoma was measured in mice. The B/I ratio was lower and the forms of hCG were less negatively charged in late pregnancy compared with early pregnancy. The lower B/I ratio might be due to the higher MCR of hCG in the test animal in the in vivo bioassay. The B/I ratio in choriocarcinoma was higher than in early pregnancy. However, the median charge of hCG was almost identical in these two groups. The most negatively charged forms of hCG were found in the men with testicular tumours. The four groups: early pregnancy, late pregnancy, gestational choriocarcinoma, and testicular tumours could be differentiated by measuring the median charge and the B/I ratio of hCG in serum. The production, later in pregnancy, of forms of hCG which disappear faster from the circulation might partially explain the lower hCG concentration in serum at this stage of gestation.Minor differences in the molecular structure of a glycoprotein hormone may be observed by com-

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Wide

Hobson²

1987

Acta Endocrinologica

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“…The serum levels of free hCG␤ correlate not only with the size of the tumor, but also with the malignant potential of the gestational trophoblastic diseases, because it has been shown that more free hCG␤ is secreted by malignant trophoblastic cells than by normal placental trophoblasts. Occasionally, malignant trophoblastic tumors secrete mostly free CG␤ and almost no intact hCG (11)(12)(13)(14).…”

mentioning

confidence: 99%

Transfection of Antisense Chorionic Gonadotropin β Gene into Choriocarcinoma Cells Suppresses the Cell Proliferation and Induces Apoptosis

Hamada

Nakabayashi

Sato

et al. 2005

The Journal of Clinical Endocrinology & Metabolism

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“…In contrast, no significant difference was found when serum hCG was measured during pregnancy with an immunometric assay for hCG or total hCGß [24]. The discrepancy was probably due to the higher production rate of the naturally occuring hCGß in ChCA than during pregnancy, resulting in a higher ratio of hCGß/hCG [6][7][8][9][10][11][12][13]. Nevertheless, immunochemical staining of the tumor for hCGß in the patient with positive total hCGß in serum was found to be negative [4].…”

Section: Discussionmentioning

confidence: 99%

“…This is, however, a technical problem which can readily be solved by validating the assay. As the secretion of free subunit of hCG (naturally occurring hCGß) and its ratio to hCG in patients with ChCA was found to be higher than during pregnancy [6][7][8][9][10][11][12][13], it was postulated that the determination of total hCGß (hCG plus hCGß) in an additive manner would be more advantageous than that of hCG or hCGß by a competitive immunoassay.…”

Section: Introductionmentioning

confidence: 99%

Fallacious hCGß in patients with choriocarcinoma. Zweifelhafte hCGß-Sekretion bei Patientinnen mit Chorionkarzinom

Dericks-Tan¹,

Taubert²

1993

LaboratoriumsMedizin

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The serum level of hCG and total hCGß (hCG plus hCGß) was measured by a manual (hCG, and ß,) and an automated (hCG 2 and ß 2 ) immunometric assay in two therapyresistant patients with choriocarcinoma (ChCA). In contrast to hCG, and hCG 2 , the results ofß, and ß 2 differed clearly. Total hCGß was always higher than hCG. The ratio of total hCGß/hCG in patientA with initially high serum hCG ranged between 7.7 and 5.3, while that ofpatient B with Iow serum hCG increased with time ranging between 7.7 and 550. The qualitative analysis of the hCG-and hCGß-activities was performed by gel chroma--tography of serum samples on during various stages of the disease, and compared to the pattern of gel chromatography of nonradioactive hCG and hCGß or serum from a pregnant woman. After gel chromatography of serum samples from the two patients with ChCA only one fraction showed hCG-activity. There was also a yariety of total hCGß-activity representing little and big-hCG or hCGß. The total hCGß activity measured by and ß 2 in the fractions obtained by gel chromatography of serum samples showed different patterns, The hCG-activity in the gel chromatogramm of the serum samples ofpatient B decreased with progress of the disease, whilst the total hCGß-activities increased in the eluates. It was concluded that the discordant measurements of total hCGß in ChCA were probably not due to hCGß but to heterogeneity in the secretory pattern of hCG-and hCGß-like substances, which also varied with time. Moreover, the total. hCGß-activities measured with different methods were shown to be considerably at variance. Keywords: hCGß -total hCGß -choriocarcinoma -gel chromatography -serum Zusammenfassung: Die Serumkonzentrationen von hCG und Gesamt-hCGß (hCG+hCGß) wurde mit manuellen (hCG, und ß,) und automatisierten (hCG 2 und ß 2 ) immunometrischen Verfahren an Blutproben von zwei Frauen mit einem Therapie-resistenten Chorionkarzinom bestimmt. Die Ergebnisse des hCG, und hCG 2 unterscheiden sich kaum voneinander, während ß, und ß 2 große Unterschiede aufwiesen. Die Konzentration des Gesamt-hCGß lag jedoch stets höher als die des hCG. Das Verhältnis von Gesamt-hCGß/hCG schwankte bei der Patientin A (mit anfänglich hohem hCG) zwischen 7,7 und 5.3, bei Patientin B (mit konstant niedrigem hCG) zwischen 7,7 und 550. Bei der letzteren nahm die Serumkonzentration von Gesamt-hCGß, nachdem es zur Metastasierung gekommen war, bei Verwendung von ß" vor allem aber von ß z/ stark zu, während hCG, und hCG 2 gleichbleibend niedrig blieb (<26 IE/1). Eine qualitative Analyse des Gesamt-hCGß und hCG im Serum wurde mit Hilfe der GelChromatographie über Sephadex-GWO und Superdex 75 während verschiedener Stadien der Erkrankung durchgeführt, und mit dem Elutionsprofil nicht-radioaktiven hCG und hCGß bzw. dem Serum einer Schwangeren verglichen. Nach der Gel-Chromatographie der Seren dieser Patientinnen wies nur eine Fraktion hCG-Aktivität auf, deren Elutionsprofil dem des authentischen hCG oder Serum einer Schwangeren glich. Dazu kam noch ein weites Spektrum von Gesam...

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Detection of the Free Beta Subunit of Human Chorionic Gonadotropin (Hcg) in Cultures of Normal and Malignant Trophoblast Cells, Pregnancy Sera, and Sera of Patients With Choriocarcinoma

Cited by 61 publications

References 6 publications

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

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

Transfection of Antisense Chorionic Gonadotropin β Gene into Choriocarcinoma Cells Suppresses the Cell Proliferation and Induces Apoptosis

Fallacious hCGß in patients with choriocarcinoma. Zweifelhafte hCGß-Sekretion bei Patientinnen mit Chorionkarzinom

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