Avaliação de bioensaios para a determinação da atividade biológica da gonadotrofina coriônica humana (hCG) / Evaluation of bioassays for measuring the of biological activity of Human Chorionic Gonadotropin (hCG)

A atividade biológica de um hormônio é mensurada pela sua capacidade em exercer um determinado efeito biológico que possa ser quantificado. Os ensaios biológicos in vivo que avaliam a atividade do hCG baseiam-se na sua capacidade de promover um aumento de peso do sistema genital, vesículas seminais e próstata em ratos impúberes e útero e ovários em camundongas impúberes. A partir destes efeitos, determinam-se equações relacionando as doses de hCG administradas com o aumento de peso do sistema genital. O objetivo do presente estudo foi avaliar a eficiência de bioensaios em mensurarem a atividade biológica do hCG utilizando ratos, ratas e camundongas impúberes. No experimento 1, ratos receberam 0, 4, 8 ou 16UI de hCG, a cada 24 horas, durante 4 dias. A próstata e/ou as vesículas seminais foram pesadas 24 horas após a última injeção. No experimento 2, camundongas receberam 0, 3,33, 10, 33,3 ou 100UI de hCG, em um único dia. Os ovários e/ou útero foram pesados 24horas após a última injeção. O hCG promoveu aumento de peso do sistema genital de camundongas, entretanto, não houve associação linear ou quadrática significativa entre as doses de hCG utilizadas e os pesos das variáveis medidas, impossibilitando a determinação de equações confiáveis. Os protocolos testados, com as doses de hCG utilizadas demonstraram eficiência e sensibilidade limitadas para a quantificação da atividade biológica do hCG.

Biological activity of a given hormone is measured by its capacity to exert a specific, quantifiable biological effect. Aim of biological assays that measure activity of hCG is to construct prediction equations that associate increasing doses of hCG with changes in weights of genitalia, seminal vesicles and prostate gland in pre-pubertal male rats and weights of uterus and ovaries in pre-pubertal female mice. Objective of the present study was to evaluate efficiency of bioassays which used pre-pubertal male rats and female rats and mice to measure hCG activity. In experiment 1, male rats received 0, 4, 8 or 16IU of hCG daily, for 4 days. Prostate and seminal vesicles were weighed 24 hours after last injection. In experiment 2, female mice received 0, 3.33, 10,33.33 or 100IU of hCG in one day. Ovaries and uteri were weighed24 hours after the last injection. The hCG increased weights of genitaliain female mice. However, there were no satisfactory linear or quadratic associations between doses of hCG used and variables measured. Itwas concluded that assays tested showed only limited efficiency and sensibility to quantify hCG biological activity.

Collagenase-IV in human trophoblast invasion and differentiation.

Trophoblast cells are unique with respect to their functions and responsibilities. These cells demonstrate three sequential phenotypes, proliferation and invasion into the endometrium, differentiation to form syncytia and endocrine secretions. Equipped with these properties placental trophoblasts are endowed with a variety of functions, like implantation of the blastocyst to the endometrium, providing nutrition to the developing embryo and also transmitting extraordinary array of signals for the embryonic development. Experimental evidences and logical extrapolation suggest that these functions are precisely controlled by growth factors, cytokines and hormones produced either by the trophoblast themselves or by the utero-placental unit. Any error in this control mechanism has extremely adverse consequences. The cells also synthesize a large number of enzymes, amongst which collagenase type IV secretion is involved in digestion of underlying basement membrane necessary for the process of invasion. Our results implicate the enzyme in the functional differentiation of the trophoblast as well. Inhibitors to this enzyme inhibit trophoblast differentiation as monitored by secretion of hCG and progesterone, the two markers of trophoblastic differentiation. In contrast, BeWo cells, a choriocarcinoma cell line which does not differentiate spontaneously, undergo increased proliferation when challenged with EGF. The results indicate the possibility of invasive and differentiative phenotypes to be coupled. Exact molecular involvements in this coupling process are looked into.

Valoración de alfa fetoproteína y gonadotropina coriónica en el diagnóstico de 290 tumores germinales testiculares / Evaluation of alpha-fetoprotein and chorionic-gonadotropin in the diagnosis of 290 testicular germinal tumors

Desde el punto de vista terapéutico y pronóstico, los tumores germinales de testículo se dividen en seminoma puro y no seminoma. El diagnóstico definitivo toma en cuenta la histología, la presentación clínica, y los niveles séricos de alfa fetoproteína (AFP) y fracción beta de gonadotropina coriónica humana (HGC). Objetivo: Correlacionar los valores de AFP y HGC con la variedad histológica y etapa clínica para determinar si cambia el diagnóstico final del tumor. Material y métodos: Se tomó suero en la valoración inicial de 290 pacientes con tumores germinales testiculares determinando niveles de AFP y HGC (ELISA, Quantum II de Abbott). Se revisaron los expedientes para conocer estirpe histológica y estadio clínico. Se consideraron seminomas los tumores con histología de seminoma puro sin elevación de AFP y HGC menor de 500 mUI/ml; los tumores germinales no seminomatosos de testículo (TGNST) presentaron histología de no seminoma o de seminoma con elevación de AFP o HGC mayor de 500 mUI/ml. Resultados: Histológicamente se encontraron 120 seminomas puros y 170 TG-NST. Se reclasificó a 13 casos de seminomas como TGNST ya que 10 presentaron elevación de AFP (tres AFP únicamente y siete AFP más HGC) y tres casos tuvieron elevación de HGC > 500 mUI/ml. La distribución final fue de 107 seminomas y 83 seminomas. Conclusiones: Al analizar los niveles séricos de AFP y HGC con la histopatología se obtiene el diagnóstico definitivo de la estirpe tumoral testicular mejorando la selección del tratamiento

Intracranial immature teratoma with syncytiotrophoblasts and tumor marker positive intestinal lining cells

Intracranial teratomas are rare entities that can present as a pure type or as mixed germ cell tumor. Cases of mixed germ cell tumor composed of immature teratoma and choriocarcinoma have been reported. Also, immature teratoma can be mixed with only syncytiotrophoblasts. We report a case of immature teratoma with syncytiotrophoblasts of the brain discovered in a 3-year-old male baby. Serum human chorionic gonadotrophin (hCG) was normal and serum alpha-fetoprotein (AFP) was elevated. The tumor was mainly composed of intestinal glands, and neither endodermal sinus tumor nor embryonal carcinomatous elements were found. The cells lining the intestinal glands were positive for hCG and AFP. These findings suggest that the syncytiotrophoblasts are differentiated from the endoderm and AFP is not necessarily a marker exclusive to endodermal sinus tumor or embryonal carcinoma.

Influencia del tumor testicular sobre el eje de hipotálamo, hipófisis y testículo / Testicular tumor influence on the hipothalamus-hypophisis-testicle axis

El teatículo contiene en su interior a las células germinales, que pueden producir cualquier clase de tejido o susbstancia en el organismo. Cuando existe crecimiento celular desorganizado, como en el cáncer, la gónada puede producir substancias, como la gonadotropina coriónica humana (HCG) y la alfafetoproteína (AFP), que se utilizan como marcadores de actividad tumoral. Se determinaron los valores basales de hormona luteinizante (LH), hormona foliculoestimulante (FSH), HGC y AFP e cuatro pacientes con tumor testicular. En tres de ellos el informe histopatológico indicó teratocarcinoma. En estos pacientes los niveles de HGC y AFP se encontraron elevados, en tanto que las gonadotropinas hipofisarias se hallaron bajas: en un paciente con diagnóstico de atrofia testicular todas las determinaciones fueron normales. Se observó que en estos pacientes la HCG circulante inhibió la liberación de LH y FSH.

Manejo médico del embarazo tubario: resultados / Medical management of the tubaric pregnancy: results

Se presentan los resultados del tratamiento con metrotexato intratubario 25 mg administrados vía laparoscopia en 8 pacientes manejadas de acuerdo a un protocolo preestablecido. En 6 casos se obtuvo éxito 75 por ciento En 4 de 5 pacientes se encontró permeabilidad tubaria bilateral a la histerosalpingografía y 3 han presentado a la fecha un embarazo intrauterino

Role of calcium in secretion of chorionic gonadotropin by first trimester human placenta.

The role of calcium in regulation of secretion of human chorionic gonadotropin (hCG) by first trimester human placental minces in vitro has been investigated. Depletion of calcium in the medium by addition of EGTA resulted in a drastic decrease in the levels of immunoreactive hCG in the medium with consequent of accumulation of hCG in the tissue. Addition of A 23187 which is a calcium ionophore resulted in a dose dose dependent increase in the hCG in the medium and this stimulatory response could not be observed in the absence of calcium. Use of lanthanum (a calcium antagonist) in place of calcium in the medium used resulted in a significant decrease in the levels of hCG in the medium. Addition of veratridine (a sodium channel activator) stimulated hCG secretion in a dose dependent manner. These results suggest that calcium is essential for normal secretion of hCG by human placenta.

Immunoperoxidase study of human chorionic gonadotropin [HCG] secretion in the trophoblastic tumours

An immunoperoxidase method has been used to demonstrate human chorionic gonadotrophin [HCG] in placental site trophoblastic tumours, hydatiform moles, and choriocarcinomas. In addition to cytotrophoblast, and syncytiotrophoblast, a third form of trophoblast designated intermediate trophoblast is present during pregnancy and in trophoblastic disease. Intermediate trophoblast has distinctive immunocytochemical features that distinguish it from cytotrophoblast and syncytiotrophoblast. The localization of HCG in both intermediate trophoblast and syncytiotrophblast varies with the type of trophoblastic neoplasm, and from one specimen to another within each category of tumour. Syncytiotrophoblast may contain HCG in large amount, whereas intermediate trophoblast contains HCG focally. Cytotrophoblast is devoid of HCG except in choriocarcinoms, which may show focal weak staining for HCG, Immunoperoxidase identification of HCG has proved helpful in clarifying the histogensis of trophoblastic neoplasms and may also be of value in establishing their diagnosis and in determining their prognosis

Variations of the cAMP levels in fish ovaries: effect of human chorionic gonadotropin in vitro and of haloperidol in vivo

Se ha desarrollado un ensayo para la determinación de la actividad gonodotrópica en peces hembra, basado en la medición de las variaciones de AMPc en ovario, por medio de un método de radiocompetición proteica. Con ovarios de Cichlasoma facetum, se establecieron las condiciones para la inducción in vitro con gonadotrofina coriónica humana (hCG): 1) preincubación en 1 ml de medio a 30MC durante 60 m; 2) incubación en 1 ml de medio con HCG a 30§C durante 60 m. Este esuqema fue usado en ovarios de Betta splendens de 3-4 meses de edad sexualmente maduras. En una serie de experimentos, se determinó que 50 UI o más de hCG por tubo de incubación, producen un aumento significativo de AMPc con respecto a los controles y que la respuesta es dosis dependiente. El efecto de una inyección intraperitoneal de haloperidol, un antagonista de la dopamina, se estudió en hembras Betta splendens de 3-4 meses de edad sexualmente maduras. Con bajas dosis se observó una tendencia al aumento de AMPc (1 microng/gm de peso corporal) y con mayores dosis (10 microng/gm de peso corporal) hubo un aumento significativo luego de 6 h de la administración. No se observó respuesta a las 24 h. Este trabajo muestra que, como en otros teleósteos, la dopamina actúa como un factor inhibidor de la liberación de gonadotrofina hipofisaria (GRIF) en B. splendens, dado que la admistración de haloperidos induce un aumento de la actividad gonadotrópica

Large Mononuclear Cells in Seminoma: An Immunohistochemical Analysis of 21 Cases

Twenty-one cases of seminoma (including testicular seminoma, ovarian dysgerminoma and extragonadal germinoma) were reviewed for the cell types responsible for the production of alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG). Histologically the cases included seventeen classical seminomas and 4 anaplastic seminomas. The latter had some mononuclear and multinuclear giant cells. All 4 patients with anaplastic seminoma had elevated levels of serum AFP, and each of these cases contained AFP producing tumor cells identified by immunoperoxidase staining. All seminomas of patients with elevated serum levels of HCG were of the classical type but HCG producing tumor cells could not be identified by immunoperoxidase staining. Immunoreactivity to anti-AFP was found in some large mononuclear cells and anaplastic cells. To explain these results, we propose that the large mononuclear cell is a multipotential cell capable of differentiating into a germ cell, yolk sac and embryo, and that the anaplastic seminoma cells might represent a stage on the continuum of cellular differentiation from the large mononuclear cells to germ cells. The multinuclear giant cell does not appear to be essential for the production of either AFP or HCG in seminoma.

Actividad coriónica temprana en mujeres portadoras de D.I.U / Chronic early activity in women using I V D

Se investigó la actividad coriónica precoz en los días premenstruales por medio de la fracción ß de H.C.G. y la excreción urinaria de H.C.G. En tanto que en el grupo de portadoras de DIU inertes se detectaron signos de actividad coriónica en el 15% de los ciclos, en el grupo con DIU de cobre esa incidencia fue nula. Esto puede desempeñar algún papel en el mecanismo de la acción contraceptiva que puede ser diferente para ambos tipos de DIU