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Results for “Chorionic Gonadotropin, beta Subunit, Human”

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PubMed1997

Effects of human chorionic gonadotropin (hCG) and beta-hCG on oncostatin M release from human peripheral blood mononuclear cells in vitro.

The effects of human chorionic gonadotropin (hCG) as well as the beta-subunit of hCG (beta-hCG) in concentrations of 80,000/25,000, 500, 50, and 5 mIU/ml on in vitro release of oncostatin M (OSM) from resting or phytohaemagglutinin (PHA) activated human peripheral blood mononuclear cells (PBMC), were studied. The concentration of OSM was measured in supernatants of human PBMC by quantitative sandwich enzyme technique. The hCG in dilutions of 80,000 mIU/ml (p < 0.05) stimulated OSM secretion from PHA activated or resting (p < 0.001) PBMC, but at a concentration of 5.0 mIU/ml diminished OSM release from activated cell cultures (p < 0.05). The beta-hCG at concentrations of 25,000 mIU/ml diminished OSM secretion only from PHA-activated PBMC. The hCG and beta-hCG at very high concentrations modulated the secretion of OSM from human lymphoid cells.

Cells, Cultured↗

PubMed1983

A degradation product of circulating luteinizing hormone (beta-hCG subunit) in human semen.

Levels of beta-human chorionic gonadotropin (beta-hCG) were detected in semen under basal conditions. No significant correlation to levels of luteinizing hormone (LH) in blood was found. The beta-hCG level did not increase within 3-7 days after a 5000 IU dose of hCG was injected intramuscularly. Human chorionic gonadotropin was detected in semen only after injection. beta-Human chorionic gonadotropin in the semen represents a degradation product of circulating LH.

Chorionic Gonadotropin↗

PubMed1993

Urinary chorionic gonadotropin subunits and beta-core in nonpregnant women. A study of benign and malignant gynecologic disorders.

BACKGROUND: The presence of urinary excretion products of human chorionic gonadotropin (hCG) has been proposed as a tumor marker. To ascertain the clinical value in gynecologic cancers, the authors studied 612 nonpregnant women. METHODS: Three different assays in four clinical groups were compared: no disease, benign disease, malignant disease, and complete remission of previously treated malignant disease. The assays were for the urinary beta-core, "total" beta-hCG, and free alpha-subunit. RESULTS: Measurement of the alpha-subunit was of no obvious clinical value. In some patients with benign disease, hCG metabolites were elevated. In the 141 patients with active gynecologic malignancy the sensitivity of the total beta-hCG assay was 47% and that of the beta-core assay was 36%. The specificities were 80.3% and 90.4%, respectively. Advanced cancers generally had higher levels of total beta-hCG and beta-core. Squamous cell and poorly differentiated cervical tumors had higher levels of total beta-hCG than did adenocarcinomas and well-differentiated cervical tumors. Invasive, serous, endometrioid, and germ cell ovarian tumors had higher total beta-hCG, beta-core, and alpha-subunit levels than did borderline, mucinous, and clear cell ovarian tumors. Six of 16 patients with disease in complete remission had elevated levels. CONCLUSION: The excretion of hCG and its metabolic fragments is a common event in gynecologic cancer, but sensitivity and specificity are low, and there is little consistent relationship between tumor stage and histologic type.

Adenocarcinoma↗

PubMed2004

Transcriptional regulation of the human chorionic gonadotropin beta gene during villous trophoblast differentiation.

Expression of the trophoblast-specific subunit of human chorionic gonadotropin, CGbeta, is associated with fusion of cytotrophoblasts into a multinuclear syncytium. Here, we studied regulation of the CGbeta5 gene in trophoblasts undergoing in vitro syncytialization. Transfection of luciferase reporters harboring different lengths of the CGbeta5 upstream sequence revealed that the proximal promoter region (-345 to +114) is sufficient to govern differentiation-dependent induction. Mutational analyses suggested that two selective promoter factor (Sp) and three activating protein 2 (AP-2) recognition sequences are necessary for full activity of the promoter. During syncytialization these elements interacted with increasing amounts of the transcription factors Sp1, Sp3, and AP-2alpha in electrophoretic mobility shift assay, but only AP-2alpha binding rose upon elevation of cAMP levels with forskolin. Increasing expression of different isoforms of Sp1 and Sp3 could also be detected by Western blot analyses. Sp1/Sp3 localized to syncytial nuclei both in differentiated cultures and in term placental tissue, suggesting assembly of functional transcriptional complexes. Costaining of the transcription factors with E-cadherin on term placental sections revealed that 47 and 33% of cytotrophoblast nuclei were negative for Sp1 and Sp3, respectively. In contrast, immunohistochemistry of early tissue demonstrated expression of Sp1 in the majority of cyto- and syncytiotrophoblasts, whereas Sp3 was absent from the syncytium. Sp1 and Sp3 induced wild-type/mutant promoter constructs upon transfection in Sp-deficient SL-2 cells, indicating that the Sp elements function as activating sequences. The data suggest that increasing concentrations of Sp1, Sp3, and AP-2alpha enhance transcription of CGbeta in differentiating term trophoblasts, whereas a different combination of factors may control expression in early placentas.

Base Sequence↗

PubMed1995

Mediastinal teratoma and precocious puberty in a boy with mosaic Klinefelter syndrome.

We describe a boy who developed precocious puberty resulting from chorionic gonadotropin produced by a mediastinal germ cell tumor. Following tumor removal he began spontaneous precocious sexual development which was treated and then arrested spontaneously. Investigation of this arrested puberty established that he had Klinefelter syndrome (KS) mosaicism. He represents the first instance of KS mosaicism reported with a mediastinal germ cell tumor, a neoplasm commonly reported in males with a 47,XXY karyotype. We recommend that all males with KS and early sexual development or with "normal" testicular growth be screened with measurement of germ cell tumor markers including beta-subunit of human chorionic gonadotropin and alpha-fetoprotein.

Child↗

PubMed1995

[Immuno-contraceptive vaccines].

Results of studies on birth control vaccines accomplished by many research groups within the WHO Special Programe of Research, Development and Research Training in Human Reproduction has been reviewed. The mostly investigated contraceptive vaccines contain human chorionic gonadotropin, and therefore structure, biological role and immunogenicity of the hormone were presented. Also, vaccines obtained on the basis of subunit beta of the human chorionic gonadotropin, its heterodimer with subunit beta of ovine lutropin or C-terminal peptide of beta subunit were described. Results of two phases of clinical trials with immuno-contraceptive vaccines were presented. The use of contraceptive vaccines for treatment of some trophoblastic tumors and the idea of using contraceptive recombinant vaccines were also mentioned.

Animals↗

PubMed1987

Detection of a glycosylated, incompletely folded form of chorionic gonadotropin beta subunit that is a precursor of hormone assembly in trophoblastic cells.

The alpha and beta subunits of human chorionic gonadotropin are secreted both as a combined, noncovalently linked dimer form as well as uncombined, free forms by human trophoblastic cells. We have utilized the cultured choriocarcinoma cell line JAR to determine what regulates the combination of the two subunits. The human chorionic gonadotropin subunits produced by JAR cells were biosynthetically labeled with [35S] cysteine or [3H]mannose by a pulse-chase protocol, purified by immunoprecipitation with specific antisera that recognize free or combined subunits, and separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under nonreducing or reducing conditions. Radioactively labeled bands were eluted from the gels and analyzed for total counts/minute incorporated, the ratio of free thiols to intramolecular cystine disulfides, and oligosaccharide composition. In some experiments, labeled gel bands were eluted with trypsin under nonreducing conditions, and the trypsin-released peptides were analyzed by high performance liquid chromatography. Using these procedures, the following results were obtained. The earliest, biosynthetically labeled form of the beta subunit detected in JAR cells contains high mannose N-linked oligosaccharides and has one-half of its incorporated cysteines present as free thiols. This form, termed pre-beta 1, has not yet combined with the alpha subunit even though the biosynthetically labeled alpha subunit is present in the cells at the same time. The pre-beta 1 form has a t1/2 of about 4 min and has a precursor-product relationship with a more completely disulfide-bonded form, termed pre-beta 2, which does combine with the alpha subunit to form a dimer. A subset of beta molecules produced in JAR cells does not attain the same disulfide bonding pattern as the pre-beta 2 form, does not combine with the alpha subunit, and is secreted as a free beta subunit into the culture medium. On the other hand, the earliest detectable form of the alpha subunit in JAR cells has all its thiols present as cystine disulfides, at a time when dimerization with the beta subunit has not yet taken place. These results strongly suggest that intramolecular disulfide bond formation in the beta subunit is the crucial and rate-limiting event in alpha beta dimer formation. The subset of beta molecules that remain free do not appear to form the appropriate intramolecular disulfides and thus do not achieve the correct conformation to combine with the alpha subunit.(ABSTRACT TRUNCATED AT 400 WORDS)

Cell Line↗

PubMed1984

The beta chorionic gonadotropin-beta luteinizing gene cluster maps to human chromosome 19.

We used a cloned human cDNA probe homologous to the placenta chorionic gonadotropin beta subunit (CGB) and to the pituitary luteinizing hormone beta subunit (LHB) and Southern blotting techniques to analyse DNA from a series of rodent X human somatic cell hybrids for the presence of specific gonadotropin beta subunit related sequences. Our results provide evidence for the assignment and linkage of the eight genes (or pseudogenes) coding for the beta subunit of these glycoprotein hormones to chromosome 19. Moreover, we observed a strict concordance between the permissivity of mouse X man hybrid cells to enteroviruses (which is linked to the presence of specific cell receptors encoded by human chromosome 19) and the presence of CGB and LHB related sequences, thus confirming the localization of the structural genes for the beta subunits on chromosome 19.

Animals↗

PubMed1981

The clinical significances of carcinoembryonic proteins in patients with ovarian carcinoma.

Carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), placental alkaline phosphatase (ALP4), human chorionic gonadotropin (HCG), human chorionic gonadotropin-beta-subunit (beta-HCG) and human placental lactogen (HPL) were simultaneously and serially determined in the sera of the patients with ovarian carcinoma. The incidence of patients whose tests for carcinoembryonic proteins were positive was as follows: CEA, 29/55 (56.4%); AFP, 7/58 (13.5%); ALP4, 3/47 (6.4%); HCG, 20/50 (40%); beta-HCG, 13/50 (26%); HPL, 0. Determination of CEA in serum was considered to be a useful test for screening ovarian carcinoma and for follow-up studies, especially for so-called mucin-producing tumors (mucinous cystadenocarcinoma, Krukenberg's tumor, and pseudomyxoma peritonei). The specificity of AFP to ovarian carcinoma, especially in tumors of germ cell origin, seemed to be very high, thus AFP can be an extremely effective means for the diagnosis and the prognosis of patients with ovarian tumors arising from germ cells. But pure dysgerminoma, which was not positive in AFP, showed relatively high levels beta-HCG preoperatively, and its clinical course was associated with serial beta-HCG assay. There was no tumor specificity in positive HCG. ALP4 seemed to have little clinical significance because the detection was infrequent.

Adolescent↗

PubMedDate not supplied

Generation of monoclonal antibodies to human chorionic gonadotropin by a facile cloning procedure.

A facile hybridoma procedure has been used to generate monoclonal antibodies to alpha- and beta-subunits of human chorionic gonadotropin (HCG). The procedure is based on the method of Davis et al. (1982, J. Immunol. Methods 50, 161) and involves the use of a semisolid medium containing methylcellulose for the initial cloning of hybrid cells following immunization and cell fusion. Seven to ten days after cell fusion, viable hybrid clones were removed for subculture in a liquid medium containing RPMI 1640 and 15% fetal calf serum. Initial screening of hybrid cell lines that secrete antibodies to HCG was performed on microplate enzyme-linked immunoassay (ELISA) using HCG-coated microtiter plates. The specificity of these antibodies to either alpha- or beta-subunits was determined by the sodium dodecyl sulfate-gel/protein blot radioimmunobinding method which separates alpha- and beta-subunits of HCG on nitrocellulose strips for radioimmunobinding assay. As a result of this study, it has been possible to generate about 272 hybrid cell lines that secrete antibodies reacting with either the alpha- or beta-subunit of HCG in about 5 weeks. The association constants and cross-reactivities to luteinizing hormone for some of the HCG monoclonal antibodies were determined. The high affinity and specificity of these monoclonal antibodies permit their clinical application in a sensitive sandwich solid-phase enzyme-linked and radioimmunoassay of HCG.

Animals↗

PubMed1986

Effective separation of human chorionic gonadotropin subunits by high performance gel permeation chromatography.

Human chorionic gonadotropin (hCG) was effectively separated into alpha and beta subunits by treating with 8 M guanidine hydrochloride, followed by high performance gel permeation chromatography (GPC) on a 2.5 X 60 cm TSK G 3000 SW column in 6 M guanidine hydrochloride. Their molecular weights estimated by GPC were about 29,000 daltons for the beta subunit and 19,000 daltons for the alpha subunit. Both subunits were examined for SDS-polyacrylamide gel electrophoresis, amino acid analyses and radioimmunoassay, respectively. Neither subunit showed significant binding to the hCG-receptor fraction of rat Leydig cell in vitro. However, the separated subunits easily recombined and recovered about 90% of receptor binding activity of intact hCG. The present results indicate that the GPC technique is an effective, simple and non-denaturing method for the separation of hCG into alpha and beta subunits.

Amino Acids↗

PubMed1993

Characterization of the 48.5 kDa chorionic gonadotropin-like protein from Xanthomonas maltophilia.

Our laboratory has previously reported the isolation of a 48.5 kDa membrane protein from Xanthomonas maltophilia (ATCC 13637) which immunologically cross-reacts with the beta-subunit of human chorionic gonadotropin (hCG) in both polyclonal and monoclonal radioimmunoassays (RIA) (1). The protein showed no reaction in RIAs for human LH, TSH, or the free alpha subunit of hCG. We have now improved the protein purification procedure and have obtained adequate bacterial protein to characterize the pure protein (designated xCG) in RIAs and also to obtain amino acid composition and partial sequence. We present these data and compare homology to hCG. An RIA for the bacterial protein has also been developed.

Amino Acid Sequence↗

PubMed1992

Monoclonal antibodies to beta subunit of choriogonadotropin: development and use in a sandwich ELISA pregnancy test.

Balb/c mice were immunized with beta subunit isolated and purified from crude human chorionic gonadotropin preparations. Spleen cells from the higher titered mouse were fused with Sp 2/0 myeloma cells. Four specific secreting hybridomas were obtained. Specificity, affinity, and suitability of secreted antibodies for use in enzyme immunoassays were studied. Ascites of the selected hybridoma was raised; the antibody was purified by protein A-affinity chromatography and coupled to horseradish peroxidase. This conjugate was employed in a simultaneous sandwich enzyme immunoassay on microtiter plates sensitized with goat polyclonal antibody to measure the hormone. The test has a sensitivity of 10 mlU/ml either on urine, serum, or plasma samples when read in a microplate reader. The results can also be evaluated by the naked eye, with a sensitivity of 20 mlU/ml. No cross reactivity was detected with other human gonadotropins.

Animals↗

PubMed1980

Inhibition of asparagine-linked glycosylation by incorporation of a threonine analog into nascent peptide chains.

The importance of threonine in the Asn-X-Thr recognition sequence for asparagine-linked glycosylation was tested by examining the effect of a threonine analog, beta-hydroxynorvaline, on co-translational glycosylation in Krebs' II ascites tumor lysates. beta-Hydroxynorvaline inhibited the glycosylation of the alpha subunit of human chorionic gonadotropin and the beta subunit of bovine luteinizing hormone; both proteins contain Asn-X-Thr recognition sites. The effect was prevented by threonine, indicating that beta-hydroxynorvaline acted via its incorporation into protein. These results provide direct evidence for the role of threonine in Asn-X-Thr sites for asparagine-linked glycosylation. The results support the view that this site is sensitive to steric hindrance.

Animals↗

PubMed2006

Apoptosis and tumor inhibition induced by human chorionic gonadotropin beta in mouse breast carcinoma.

For many breast cancer patients, human chorionic gonadotropin beta (hCGbeta), which is a subunit of a hormone produced by the trophoblast and is essential for maintaining pregnancy, is expressed in the breast cancer cells. However, the mechanism as to how the CGbeta in cell affects the cancer development is not very clear. Mouse breast carcinoma 4T1 with stably hCGbeta expression (4T1-hCGbeta) was established and transplanted into the Balb/c mouse abdominal mammary gland. hCGbeta suppressed breast cancer cell viability in vitro, and dramatically inhibited tumor growth and attenuated tumor vessel formation in vivo. An 86-88% reduction in tumor volume in animals injected with breast cancer expressing hCGbeta, as opposed to those injected with breast cancer without hCGbeta expression, was observed. The production of p21 was promoted by hCGbeta, whereas the Cdk2 was decreasing. These indicate that p21 signal pathway is involved in this process. Significant apoptosis was also detected in hCGbeta-expressing breast cancer cells as well as the enhancement of Bax protein expression. Moreover, hCGbeta blocked the blood vessels formation by inhibiting the expression of MMP9 and VEGF. Further hormone secretion analyses show that the anti-tumor activity induced by hCGbeta is not related to the endocrine function.

Animals↗

PubMed2000

Secretion of hCG/beta-hCG by squamous cell carcinoma of the lung in a 31-year-old female smoker.

We describe a rare case of pulmonary squamous cell carcinoma secreting human chorionic gonadotropin (hCG) and its beta-subunit (beta-hCG) in a young female smoker. A 31-year-old mother of one child had been suffering from dysfunctional uterine bleeding for about 1 year. Pelvic examinations and abdominal ultrasonography yielded no abnormal findings and no signs of pregnancy. She developed a pain in the right chest and a huge (12x10 cm) squamous cell carcinoma was diagnosed in the right lower lobe. The serum hCG and beta-hCG levels were high: hCG 5611 mlU/ml (normal upper limit 0.7 mIU/ml), beta-hCG 12 238 mIU/ml (normal upper limit 0.5 mIU/ml). The patient underwent right lower lobectomy and systematic lymph node dissection. Microscopic study showed a poorly differentiated squamous cell carcinoma. The pathological stage was T2N0M0, stage IB. Immunohistochemical staining of the tumor was strongly positive for hCG. The serum hCG level returned to normal 1 month after the operation, while an additional 2 months were necessary for the beta-hCG level to normalize. Dysfunctional uterine bleeding disappeared and the patient is doing well, with no signs of recurrence, 9 months after the resection.

Adult↗

PubMed1990

[Diagnostic value of tumor markers in pleural effusions].

In order to discriminate between benign and malignant effusions, the value of alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and beta subunit of human chorionic gonadotropin (GNCH Sub-beta) has been estimated in pleural exudates. A sample of 65 patients, 33 with a malignant (histologically and/or cytologically established) and 32 with a benign effusion was analysed. Only mean CEA in malignant effusions was significantly higher than in benign effusions (p less than 0.01). In the detection of malignant effusion CEA showed a sensitivity of 57% and a specificity of 97%; AFP a sensitivity of 9% and a specificity of 97% and GNCH Sub beta a sensitivity of 9% and a specificity of 90%.

Adolescent↗

PubMed1985

Radioimmunolocalization of monoclonal antibodies to human chorionic gonadotropin in choriocarcinoma transplanted into athymic mice.

Radioimmunodetection of monoclonal antibodies to human Chorionic Gonadotropin (hCG) or its beta-subunit in choriocarcinoma tissue was investigated in athymic mouse model system. Antibody to hCG exhibited a higher localization index (L.I.) in tumor tissue than those in other organs, but the tissue/blood ratio of this antibody in tumor tissue was not so high as expected (0.38 and 0.5 on Day 2 and 5 respectively). On the other hand, antibody to beta-subunit showed the same L.I. in tumor tissue as those in other organs. Gel filtration of serum of mouse given an antibody to hCG showed that the antibody was forming immune complexes in the blood stream. Autoradiography showed many grains in the capillary vessels and intercellular spaces in the tumor tissue. We concluded that a monoclonal antibody to hCG localized in choriocarcinoma tissue via a mechanism of retention of immune complexes in the tissue, and that there may be a limitation to the clinical application of localization of antibodies to secretory products such as hCG of tumor cells from their low specific localization.

Animals↗