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Falsely positive specific human chorionic gonadotropin assays in patients with testicular tumors: conversion to negative with testosterone administration.

We report false elevations of serum human chorionic gonadotropin levels in 4 patients with testicular germ cell tumors. Elevated circulating luteinizing hormone levels that resulted from unilateral orchiectomy were responsible for the falsely positive human chorionic gonadotropin activity measured in commercial radioimmunoassays. In 3 patients tested aliquots of serum evaluated in reliable human chorionic gonadotropin assay systems revealed no elevation. We administered testosterone to 3 patients who had elevations of luteinizing hormone and human chorionic gonadotropin levels. Luteinizing hormone was suppress-d to normal levels 1 week later in 2 patients and in 1 it was diminished but still slightly elevated. In all 3 cases the falsely positive human chorionic gonadotropin results converted to negative. Recognition of falsely positive elevations of human chorionic gonadotropin can spare patients unnecessary operations and/or chemotherapy.

Adult

Structures of the asparagine-linked sugar chains of human chorionic gonadotropin.

The asparagine-linked sugar chains of human chorionic gonadotropin were released from the polypeptide moiety by hydrazinolysis followed by N-acetylation and NaB3H4 reduction. More than 90% of the released radioactive oligosaccharides contained N-acetylneuraminic acid residues. After removal of N-acetylneuraminic acid residues by sialidase treatment, two neutral oligosaccharide fractions were obtained by paper chromatography. Sequential exoglycosidase digestion revealed that one of them was a mixture of two neutral oligosaccharides. The complete structures of the three oligosaccharides were elucidated by methylation analysis. It was confirmed that all the N-acetylneuraminic acid residues of the asparagine-linked sugar chains of human chorionic gonadotropin occur as NeuAc alpha 2 leads to 3Gal groupings by comparing the methylation analysis data for the acidic oligosaccharide mixture before and after sialidase treatment. Based on these results, the structures of the asparagine-linked sugar chains of human chorionic gonadotropin were confirmed to be +/- NeuAc alpha 2 leads to 3Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 6(NeuAc alpha 2 leads to 3Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4(+/- Fuc alpha 1 leads to 6)GlcNAc and Man alpha 1 leads to 6(NeuAc alpha 2 leads to 3 Gal beta 1 leads to 4 GlcNAc beta 1 leads to Man alpha 1 leads to 3)Man beta 1 leads to 4 GlcNAc beta 1 leads to 4GlcNAc.

Asparagine

Interactions of bovine thyrotropin and human chorionic gonadotropin with adenylate cyclase in bovine thyroid membranes.

Previous studies have shown that crude preparations of human chorionic gonadotropin bind to bovine thyroid membranes, displace 125I-labeled bovine thyrotropin therefrom, and are weak agonists therein with respect to the activation of adenylate cyclase. The present studies reveal that concentrations of chorionic gonadotropin sufficient to elicit a maximal agonistic response of adenylate cyclase are strongly antagonistic to the stimulatory action of bovine thyrotropin in the thyroid membrane system. This effect is reminiscent of the inhibitory effects of crude human chorionic gonadotropin on other extragonadal tissues in vitro, and, like them, appears to be mediated by some factor(s) other than human chorionic gonadotropin itself, since highly purified human chorionic gonadotropin was without effect.

Adenylyl Cyclases

The modulating effect of human chorionic gonadotropin on lymphocyte blastogenesis.

Human chorionic gonadotropin (HCG) produced by fetal trophoblastic cells was suggested to play a role in the suppression of maternal lymphocyte response against the fetal allograft. Reports supporting this concept have demonstrated a suppressive effect of crude HCG on lymphocyte blastogenesis. However, similar doses of purified hormone preparations were unable to inhibit lymphocyte stimulation with mitogens. A modulating influence of phenol-free and immunoglobulin-free HCG preparation on lymphocyte blastogenesis is presented. Enhanced lymphocyte stimulation with various mitogens occurred in cultures supplemented with HCG at low doses. On the other hand, higher hormone concentration exerted an inhibitory effect on lymphocyte blastogenesis. An increase in lymphoid cell concentrations was demonostrated in cultures supplemented with the hormone preparation. These observations are compatible with the suggested role of HCG in the maternal tolerance toward a histoincompatible fetus.

Animals

Variability in β-human chorionic gonadotropin concentrations following evacuation of a hydatidiform mole pregnancy: A retrospective cohort study from Vietnam.

BackgroundGestational trophoblastic disease refers to a group of tumors defined by abnormal trophoblastic proliferation. This disease produces a distinct tumor marker, beta-human chorionic gonadotropin, which can be useful for diagnosis and follow-up. The objective of this study was to investigate the variations in serum beta-human chorionic gonadotropin levels after uterine evacuation as well and the progression of gestational trophoblastic neoplasia.Materials and methodsThis retrospective cohort study was conducted at Tu Du Hospital, Vietnam, between January 2019 and December 2020. All patients diagnosed with molar pregnancy were analyzed retrospectively based on serial serum beta-human chorionic gonadotropin levels following uterine evacuation. Post-evacuation outcomes, including relapsed molar pregnancy and gestational trophoblastic neoplasia, were also monitored.ResultsWe enrolled 560 patients with molar pregnancy, including 298 with complete hydatidiform mole and 262 with partial hydatidiform mole. Severe symptoms were more common in those with complete hydatidiform mole. Over the follow-up period, 97 cases of gestational trophoblastic neoplasia were noted. The data show that the median time to gestational trophoblastic neoplasia diagnosis was 8.75&#x2009;&#xb1;&#x2009;4.41 (4-26) weeks. In terms of variations in the serum beta-human chorionic gonadotropin levels, the generalized estimating equation model showed a faster decline in the complete hydatidiform mole group than in the partial hydatidiform mole group. Similarly, regression in serum beta-human chorionic gonadotropin levels was significantly more rapid in patients who progressed to gestational trophoblastic neoplasia than in those with relapsed molar pregnancy (-11,593 vs. -20,651.22 and -12,946.26 vs. -46,329.23 mUI/mL, p&#x2009;<&#x2009;0.001).ConclusionsSurveillance of serum beta-human chorionic gonadotropin levels remains essential for gestational trophoblastic neoplasia monitoring in patients with molar pregnancy following surgical evacuation. The post-evacuation serum beta-human chorionic gonadotropin level regression curve helps distinguish gestational trophoblastic neoplasia from hydatidiform moles. Further evidence is required to strengthen these findings.

Humans

[The excretion of chorionic gonadotropin in ectopic pregnancy (author's transl)].

In 244 cases of ectopic pregnancy the excretion of chorionic gonadotropin in the urine was determined in 459 tests. In 88% of the cases an immunologic pregnancy test (pregnosticontest) was positive. The mean quantitive excretion of chorionic gonadotropin in the urine was 20 +/- 13% of the values for normal pregnancy. In 11.4% of the cases, values compatible with the chorionic gonadotropin excretion in normal intra-uterine pregnancy were observed. Repeat quantitative tests on the same patient showed a decrease of the mean chorionic gonadotropin titre in the urine with increasing gestational age. The results are shown in diagrams.

Chorionic Gonadotropin

Alpha-fetoprotein and human chorionic gonadotropin in the management of testicular tumors.

Alpha-fetoprotein and human chorionic gonadotropin levels were measured by radioimmunoassays in 260 patients with genitourinary diseases, including 93 patients with testicular tumors. Elevations of alpha-fetoprotein and human chorionic gonadotropin were associated only with non-seminomatous germ cell testicular tumors. Our 32-month experience with serial measurements of the 2 markers in patients with these tumors shows that alpha-fetoprotein and human chorionic gonadotropin must be determined and that together they serve as accurate and sensitive indicators of metastases and are helpful in determining the effectiveness of therapy. However, they have limited value in the differential diagnosis of scrotal masses.

Adult

Duration of chorionic gonadotropin production by the placenta of the rhesus monkey.

Concentrations of macaque chorionic gonadotropin (mCG) in placenta, blood and urine of rhesus monkeys have been measured by both radioimmunoassay and bioassay throughout gestation. mCG was easily detected and quantified in these specimens for a brief period in early pregnancy, but was not detectable between the 40th day of pregnancy and term in placental extracts, serum, or 40-fold urine concentrates. The apparent absence of mCG after the 40th day of pregnancy makes these macaques a valuable model for pregnancy research, where the absence of chorionic gonadotropin is experimentally desirable. Unlike women and some higher primates, the functional status of the fetal, placental and maternal endocrine compartments of macaques can be studied in the absence of circulating chorionic gonadotropin during mid and late gestation.

Animals

Pregnancy diagnosis in owl monkeys (Aotus trivirgatus): evaluation of the hemagglutination inhibition test for urinary chorionic gonadotropin.

The Subhuman Primate Pregnancy Test was evaluated as a means of detecting urinary chorionic gonadotropin to aid in pregnancy diagnosis in owl monkeys. Using radioimmunoassay, the excretion pattern of chorionic gonadotropin from pregnant owl monekys was delineated, the hormone being detected from 16 weeks prepartum until birth. By comparison, the pregnancy test kit detected chorionic gonadotropin between the fourteenth week prepartum and the last week of gestation with 94% accuracy. In a 2-year study using a simplified urine collection technique, the Subhuman Primate Pregnancy Test was shown to be a valuable procedure for diagnosing pregnancy and detecting spontaneous abortions in owl monkeys.

Animals

Diagnosis of pregnancy in marmosets: hemagglutination inhibition test and radioimmunoassay for urinary chorionic gonadotropin.

The Subhuman Primate Pregnancy Test kit was used for diagnosis of pregnancy in 17 marmosets. This hemagglutination inhibition test for urinary chorionic gonadotropin accurately indicated conception by positive responses in 72 and 76 specimens collected between the 4th and 10th wk following the estimated time of fertilization. The rate of false positive results did not exceed 1%. A radioimmunoassay system was used to quantify chorionic gonadotropin concentrations in urine. Detectable levels were present by the 2nd week of pregnancy. Peak chorionic gonadotropin levels were found between the 7th to 9th wk after conception. Chorionic gonadotropin excretion rates declined to undetectable levels during the final month of gestation.

Animals

[Demonstration and evolution of chorionic gonadotropin in ewes].

Occurrence of ovine Chorionic Gonadotropin (oCG) is demonstrated in placenta and amniotic fluid with the use of a radioreceptor assay (corpus luteum membranes) in ewes. Identification of oCG is possible as early as 15th day of pregnancy. It should be secreted at a constant rate, and its maximum concentration is recorded on the 130th day. This hormonal factor might be one of the major components accountable for high progesteronemia observed during the 100 last days of pregnancy.

Amniotic Fluid

Ectopic human chorionic gonadotropin in breast carcinoma.

Immunoreactive human chorionic gonadotropin (hCG) was found in 9 of 65 surgically removed malignant breast tumors. Concentrations ranged from 5 to greater than 500 mIU hCG/g tumor. hCG was measured by a beta-chain specific readiommunoassay. In further study of these specimens, an immunoperoxidase staining technique was used to stain for hCG in formalin-fixed sections. The hCG was shown to be localized within the cytoplasm and on the surface of the malignant cells.

Breast Neoplasms

Serum human chorionic gonadotropin levels throughout normal pregnancy.

Human chorionic gonadotropin (hCG) levels were measured in the sera of 443 pregnant women by the beta-hCG radioimmunoassay in order to determine if the third-trimester secondary peak in hCG levels observed by less specific immunoassays was due to cross-reacting substances. hCG was detected as early as six days after presumed conception and peaked between 56 and 68 days, with a nadir at 18 weeks. No secondary rise in hCG levels was demonstrated, indicating that the nonspecific hCG immunoassays give spuriously high values for hCG during the last trimester of pregnancy.

Chorionic Gonadotropin

Radioimmunoassay of rhesus monkey chorionic gonadotropin.

A radioimmunoassay for rhesus monkey chorionic gonadotropin (mCG) employing an antiovine LH antiserum, 125I or 131I-ovine LH tracer, and mCG for standards was developed. Radioimmunoassay of serum levels of mCG during pregnancy indicated that mCG began increasing as early as day 12 after mating, reached a peak by day 25, and declined to nondetectable levels around day 35. The assay procedure was adapted for use as a rapid method for pregnancy diagnosis; the results were available as early as 12 hours after collection of serum samples. The method is capable of detecting a few pregnancies by day 12 and all pregnancies by day 17. Routine use of this method provided accurate pregnancy diagnosis four days earlier than was possible with the mouse uterine weight bioassay method previously used in this laboratory.

Animals

Location of major antigenic sites of the beta subunit of human chorionic gonadotropin.

Purified beta subunit of human chorionic gonadotropin (hCG) was partially reduced with beta-mercaptoethanol, carboxymethylated, and digested with chymotrypsin. The peptides were isolated by high-voltage electrophoresis and paper chromatography. Five major disulfide-containing peptides were isolated, and their location in the parent molecule was established by amino acid composition and amino- and carboxy-terminal analyses. All of these peptides inhibited the binding of 125I-labeled hCG by anti-beta hCG serum. The inhibitory effect of these peptides was lost when their disulfide bonds were reduced and alkylated. Synthetic carboxy-terminal peptides were not inhibitory. Based on these data it is concluded that a major antigenic site of hCG resides in the region of residues 21-23 with a disulfide bond connecting cysteine-23 or -26 with the cysteines at positions 72 or 110.

Amino Acid Sequence

Suppression of luteinizing hormone in castrated women by the administration of human chorionic gonadotropin.

The suppressive effect of human chorionic gonadotropin (hCG) on luteinizing hormone (LH) and/or LH-beta was studied by specific LH-beta radioimmunoassay following hCG administration. Eight castrated women were each administered 10,000 IU of hCG in a single intramuscular injection and five women in the control group were injected with saline. The serum level of hCG increased after the injection, reaching 217.6 mIU/ml after 8 h. There was a significant suppression of LH levels as compared to those of the control group and the pre-injection levels: 68.2% 1 h after injection, 64.7% after 2h, 65.5% after 4 h, 77.0% after 8 h, 78.6% after 12 h, and 78.2% after 24 h. There was no significant suppression of the follicle-stimulating hormone (FSH) as compared to the preinjection and control values. Serum concentration of estradiol1 was not detectable either before or after the hCG injection. We conclude that hCG has a suppressive effect on LH and/or LH-beta secretion not mediated by estradiol.

Adult

Ability of human chorionic gonadotropin beta-subunit to inhibit the steroidogenic response to lutropin.

Ability of the beta-subunit of human chorionic gonadotropin to inhibit the response to lutropin (luteinizing hormone, LH) was tested in the immature rat ovarian system and pregnant-mare-serum-gonadotropin-primed rat ovarian system with progesterone production being used as the response. Human chorionic gonadotropin beta-subunit was found to inhibit human and ovine lutropin-stimulated progesterone production. At a constant dose of lutropin, inhibition was dependent on the concentration of beta-subunit. When concentration of the beta-subunit was kept constant at 5.0 microgram/ml and the concentration of lutropin was varied, the inhibition was maximum at the saturating concentration of the native hormone. The alpha-subunit of the human chorionic gonadotropin did not inhibit the response to lutropin. The lutropin/beta-subunit ratio required to produce an inhibition of response was much lower than that required to bring about an observable inhibition of binding.

Animals