Human chorionic gonadotropin in primary liver carcinoma in adults

Summary Production of human chorionic gonadotropin (hCG) by extra-gonadal tumours is not a rare phenomenon. In the liver, similar results have been reported in hepatoblastomas. The present study was attempted to survey hCG level in serum and hCG-immunoreactivity in primary liver carcinoma in adults. Although hCG was elevated in serum in 2 (22.2%) of 9 autopsied cases with hepatocellular carcinoma (HCC), the hCG-reactivity of carcinoma cells was found in 2 (2.1%) of 95 HCC cases. Carcinoma cells positive for immunoreactive hCG was found in 2 (15.4%) of 13 cases with cholangiocarcinoma (CC). The patients with hCG-immunoreactivity in carcinoma and/or elevated serum level of hCG failed to reveal distinct clinical and endocrinological disturbance due to excess hCG. The hCG-positive cells were focal within the carcinoma and showed poor histological differentiation in both HCC and CC, and there were no trophoblastic cells. It is suggested that hCG is one of the hormones produced by primary liver carcinoma in adults and can be localised immunohistochemically in a small number of poorly differentiated carcinoma cells.     

Secretion of human chorionic gonadotropin in early pregnancy

Remarkable secretion from the syncytial trophoblast of chorionic villi was observed in early pregnancy. Histology and histochemistry revealed many cytoplasmic protrusions containing numerous secretory granules, which were of basophilic glycoprotein in nature. Also, immunohistochemistry proved that these were human chorionic gonadotropin (hCG). Electron microscopy clarified the overall secretory process, which started with the production of small granules in the Golgi complex; then, the granules migrated toward the cell surface, increasing their size by fusing with each other, and gathered in cytoplasmic protrusions, then liquefied to be liberated by a mode of exocytosis into the maternal bloodstream (intervillous space). This remarkable hCG secretion, morphologically represented by the many cytoplasmic protrusions containing numerous secretory granules, arose synchronously on the surface of almost all chorionic villi. This phenomenon was limited to the eighth and ninth weeks of gestation, concurring with the maximal hCG concentration of maternal blood serum during pregnancy.     

Autoantibodies to human chorionic gonadotropin in habitual abortions

An enzyme immunoassay is developed for detecting autoantibodies to human chorionic gonadotropin in the blood serum and a high incidence of these antibodies in women with a history of habitual abortions is demonstrated. A high level of autoantibodies is associated with threatened abortion, placental dysfunction, and hemostasis disorders. The results confirm the hypothesis regarding the production of autoantibodies to human chorionic gonadotropin as a possible autoimmune mechanism underlying habitual abortion. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, No. 4, pp. 450–452, April, 1996 Presented by V. I. Kulakov, Member of the Russian Academy of Medical Sciences     

Testicular seminoma with human chorionic gonadotropin production

Testicular seminoma with elevated serum human chorionic gonadotropin level (hCG-positive seminoma) is regarded as more malignant than marker-negative seminoma, although Its prognosis is still unclear. To clarify the malignant potential of seminoma with hCG production, the serum levels of the beta subunit of hCG (β-hCG) and lactic acid dehydrogenase (LDH) were examined in 35 and 40 patients, respectively, and the Immunohistochemical expression of β-hCG examined in 45 tumors. The elevation of the LDH serum level correlated to the Invasive status, metestatic status and poor outcome, while that of the serum β-hCG level correlated only to the metastatic status. Immunohistochemical expression of β-hCG was observed in syncytiotrophoblastic giant cells in 11 tumors and a few mononuclear seminoma cells In 36 tumors. Expression was not associated with the malignancy potential, except where the expression In mononuclear cells Inversely correlated to the invasive status. These results suggest that most seminomas produce a slight amount of hCG; that an elevated hCG serum level Indicates the pressnce of metastatic tumors and mainly reflects an increase in tumor volume but not in cellular malignancy potential; and that the LDH serum level, rather than hCG, is more useful as a prognostic indicator for patients with seminoma.     

11beta-hydroxysteroid dehydrogenase inhibitor carbenoxolone stimulates chorionic gonadotropin secretion from human term cytotrophoblast cells differentiated in vitro

PROBLEM: To investigate the effect of altering local glucocorticoid concentration on human chorionic gonadotropin (hCG) production by cultured placental trophoblast cells. METHOD OF STUDY: Human placental trophoblasts were isolated from fresh placentas. Cytotrophoblasts were purified and placed into 24-well multiplates. For cultivation Dulbecco's modified Eagle's medium (DMEM) with 15 mm HEPES and 15% FBS was used. 11beta-Hydroxysteroid dehydrogenase (11beta-HSD) activity and its inhibition by carbenoxolone (CE) were measured in cultured cells. Cultures were exposed to CE for 16-20 hr. Overnight production of hCG was measured by radioimmunoassay in control and treated cells. RESULTS: The 11beta-HSD activity in these cultures was inhibited by nm concentrations of CE, the apparent Ki being 2.5 nm. Inhibition of 11beta-HSD activity with 0.1 nm CE resulted in 1.5-fold increase in the production of hCG. CONCLUSIONS: Increasing local glucocorticoid concentration by the inhibition of 11beta-HSD results in higher hCG secretion, which in turn enhance cell differentiation.     

非妊娠状态下人绒毛促性腺激素的免疫调节作用研究进展

人绒毛膜促性腺激素(HCG)可异位表达于肿瘤细胞,HCG 具有生长因子作用和抑制肿瘤细胞凋亡作用,从而在肿瘤的发生、发展、预后中发挥一定作用。HCG 作为天然的免疫调节剂是治疗自身免疫疾病的潜在药物,本文对HCG 在非妊娠期的免疫调节作用进行综述。     

Human chorionic gonadotropin in the plasma of normal, nonpregnant subjects.

To determine whether ectopic secretion of a protein hormone can occur normally, we studied plasma from normal, nonpregnant subjects for the presence of a placental hormone, human chorionic gonadotropin. We extracted and purified this hormone from other plasma proteins. We identified the hormone in the final residue on the basis of its dose-response curves in a specific radioimmunoassay and calculated the plasma concentration after correction for losses. Because this assay is sensitive to concentrations as low as 2 pg per milliliter, human chorionic gonadotropin could be detected in the plasma of 12 of 16 blood donors; the median concentration was 19 pg per milliliter (range, less than 2 to 361). This immunologic human chorionic gonadotropin was further characterized from a pool of normal plasma by gel filtration on Sephadex G-100 and was found to be identical to the standard form of the hormone. The concentration in this pool from 13 normal men was 18 pg per milliliter. The source of this ectopic hormone production is unknown, but may be normal, rapidly proliferating nonmalignant cells.     

Ectopic production of the beta-subunit of human chorionic gonadotropin in osteosarcoma

Production of human chorionic gonadotropin by sarcomas is an uncommon phenomenon that has rarely been documented. A case of a 26-year-old woman with osteosarcoma of the left fibula and high levels of serum beta-human chorionic gonadotropin (beta-HCG) is described. Immunoperoxidase staining showed numerous tumor cells reacting with the beta-HCG antibody. Immunohistochemical studies performed on ten additional osteosarcomas demonstrated another case in which some tumor cells presented immunoreactivity for beta-HCG. These results indicate that beta-HCG may be used as a marker of persistent or recurrent disease in those uncommon cases of osteosarcoma in which serum levels of beta-HCG are elevated at the onset of treatment.     

Solid-phase competitive and sandwich-type erythro-immunoassays for human chorionic gonadotropin

A simple ‘1-step’ competitive erythro-immunoassay for human chorionic gonadotropin (hCG) employing V-shaped well microtitration plates coated with monoclonal anti-β-hCG antibody has been described. hCG of the test sample competes with the antigen-coupled sheep erythrocytes for binding to the antibody on the solid surface. The assay is able to detect up to 31.25 ng hCG/ml. A higher sensitivity enabling detection up to 0.25 ng hCG/ml is attained by the sandwich erythro-immunoassay using a chimera antibody prepared by coupling monoclonal anti--hCG antibody to an affinity-purified polyclonal antibody specific for sheep erythrocytes. This assay is amenable to the qualitative as well as quantitative use as described. The urinary components do not interfere in the assay. Results obtained by this assay on 47 human urine samples correlated well with the values obtained by ‘2-step’ sandwich enzyme immunoassay and radioimmunoassay.     

Development of colorimetric enzyme-linked immunosorbent assay for human chorionic gonadotropin

The present study demonstrated the development of a solid phase competitive enzyme linked immunosorbent assay (ELISA) for direct estimation of human chorionic gonadotropin (hCG) in serum and urine. Polyclonal antisera raised against the beta- subunit of peak-I hCG was used in the assay. The Peak-IA hCG-penicillinase was used as tracer. The performance of this antiserum and tracer was compared against hCG-beta antisera of NIH, USA and penicillinase conjugated to hCG-beta obtained from NIH, respectively. Almost parallel standard curves were obtained in both cases, suggesting that these antisera and enzyme label have much potential for developing ELISA system. To the anti-rabbit gamma globulin (ARGG) coated polystyrene tubes, standard or serum or urine samples (50 microL), 100 microL of hCG-beta antiserum, 100 microL of peak-I(A) hCG-penicillinase conjugate and 350 microL of assay buffer were incubated at 37 degrees C for 2 hours. Bound enzyme activity was measured using Penicilline V as substrate. In this new strategy, locally available polystyrene tubes were ground from inside and coated with ARGG. The sensitivity of the assay was 17 mIU/mL in urine and 18 mIU/mL in serum. The intra-assay and inter-assay coefficients of variation (CVs) appeared to be within acceptable limits of 10%. The serum and urinary hCG values, obtained by this method, correlated well with those obtained by radioimmunoassay (RIA) r = 0.98 (n = 100 for serum samples; n = 250 for urinary samples).     

Expression of the alpha subunit of human chorionic gonadotropin in normal and neoplastic neuroendocrine cells. An immunohistochemical study

The alpha subunit of human chorionic gonadotropin (HCG) was localized Immunohistochemically in paraffin sections of normal human tissues and neuroendocrine tumors. A small subset of dispersed neuroendocrine cells was positive in normal adult tissues, including gastric antrum, urachal remnant, anal glands and prostate. Positive cells were consistently present in perinatal lung but rare in adult lung. In contrast, the beta subunit was absent from these cells. Seventy-two of 151 extrapituitary neuroendocrine tumors (48%) were alpha subunit-positive. Thirty-three of 37 bronchial carcinoids (92%) were immunoreactive, with a high percentage of the tumors (54%) containing moderate to large numbers of positive cells. The alpha subunit was further demonstrated in 9 of 45 small cell lung carcinomas (20%), 19 of 35 extrapulmonary carcinoids (54%), 3 of 11 islet cell tumors (27%) and 8 of 13 medullary thyroid carcinomas (62%). Two of three malignant islet cell tumors were positive. Positive cells were usually few in number, except for two small cell lung carcinomas, two rectal carcinoids, one thymic carcinoid and one malignant islet cell tumor. Pheochromocytomas (n = 10) were negative. Eleven of 19 pulmonary tumorlets (58%) were alpha subunit-immunoreactive. A few beta subunit-positive cells were detected in only 6 lung lesions. The physiological significance of the imbalance of expression of HCG subunits by certain neuroendocrine cells and their tumors remains unknown.     

Human chorionic gonadotropin does not alter patterns of adrenal androgen secretion in primary human adrenal reticularis and fasciculata cell culture

OBJECTIVE: Controversy surrounds the role of the ovary in maintaining postmenopausal androgen levels. Some postulate that aging ovaries are endocrinologically senescent and that menopausal levels of luteinizing hormone drive the adrenal cortex to secrete increasing amounts of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) as prohormones for subsequent peripheral bioconversion to maintain menopausal testosterone levels. We hypothesized that human chorionic gonadotropin (hCG), acting as an luteinizing hormone analog, would thus augment adrenal androgen secretion from primary human adrenocortical zona reticularis and zona fasciculata cell cultures. DESIGN: Human adrenal glands, obtained from a local organ donation program, were separated microscopically into reticularis and fasciculata zones and were cultured to confluence in serum-supplemented media, followed by a further incubation in defined media. They were then exposed to 24 hours of varying hCG doses, followed by an incubation with defined media and pregnenolone. Supernatants were assayed for adrenal androgens and cortisol. Data were expressed as the molar ratio of (DHEA+ DHEAS)/cortisol and the molar ratio of DHEA/DHEAS. For each of the four runs, mean molar ratios were compared by analysis of variance. RESULTS: For each of the four runs, the molar ratio was increased 17- to 157-fold in the reticularis compared with the fasciculata cells, indicating efficient zonal separation. Addition of hCG did not alter the molar ratios of adrenal androgens to cortisol or DHEA/DHEAS for either cell type. CONCLUSIONS: Addition of hCG to human adrenal reticularis or fasciculata cells does not seem to change the pattern of secretion of adrenal androgens or cortisol. It is thus unlikely that luteinizing hormone plays a significant role as an adrenal androgen secretagogue, at least with short-term exposure.     

Necessity for two human chromosomes for human chorionic gonadotropin production in human-mouse hybrids

Through a series of human-mouse hybrids we have identified that two human chromosomes, 10 and 18, must be present for production of the pregnancy protein hormone human chorionic gonadotropin (hCG). Human choriocarcinoma cells producing hCG were hybridized to mouse cells. From 49 independent clones three hybrid clones continued to produce whole hCG. Chromosomal analysis was done on the 3 producer clones and 5 nonproducer clones. The additional 41 nonproducer clones were genetically characterized by isozymes. Only when chromosomes 10 and 18 were present in a clone would the whole hCG molecule be produced. Clones with only 10 or only 18 did not produce hormone. Nine subclones of a producer clone confirmed this observation. Three subclones retaining both 10 and 18 continued to produce hCG. This study demonstrated the need to use cellular chromosome data and population enzyme data to identify two chromosomes necessary for hCG production in heterogeneous human-mouse hybrids.     

Elevated human chorionic gonadotropin levels in pregnancies with sex chromosome abnormalities

Numerous reports have dealt with the usefulness of the maternal serum alpha-fetoprotein marker (MsAFP) and human chorionic gonadotropin (MshCG) levels in the detection of Down syndrome (DS) and other autosomal trisomies. Only few reports have discussed the possible association of elevated levels of MshCG and sex chromosome aneuploidy. We wish to report on 3 cases in which this association was found. © 1993 Wiley-Liss, Inc.