concanavalin-a and Hydatidiform-Mole

This study investigates the physicochemical characteristics of human chorionic gonadotropin (hCG) in gestational trophoblastic disease (GTD), with special reference to the clinical course of chemotherapy and prognosis. In gel high performance liquid chromatography (HPLC), the hCG molecules from normal pregnancy and from the hydatidiform mole had the same molecular form as standard purified hCG, whereas hCG from choriocarcinoma was inconsistent in molecular form, containing molecules which are smaller, the same or larger than those of standard purified hCG. In two fatal choriocarcinoma patients, large hCG and large hCG alpha were found in the urine samples collected within one month prior to death. In a chromatofocusing study, the chromatofocusing pattern of hCG from GTD was acidic and similar to that of early pregnancy. The chromatofocusing patterns did not alter or were altered only slightly during the course of chemotherapy. In a Concanavalin A-Sepharose (Con A) chromatography study, the Con A binding shifted from low to high binding in patients with GTD who were responsive to chemotherapy. In summary, the molecular form, electric charge and Con A binding of hydatidiform mole hCG are similar to those of early pregnancy hCG and standard purified hCG, whereas the molecular form and Con A binding of choriocarcinoma are different from those of early pregnancy hCG and standard purified hCG. The presence of smaller or larger molecular forms of hCG may be an ominous sign, whereas the presence of high Con A binding may be a favorable sign. The chromatofocusing pattern seems to be unrelated to the clinical course of chemotherapy.

Topics: Choriocarcinoma; Chorionic Gonadotropin; Chromatography, Agarose; Chromatography, High Pressure Liquid; Concanavalin A; Female; Glycopeptides; Glycosylation; Humans; Hydatidiform Mole; Isoelectric Focusing; Pre-Eclampsia; Pregnancy; Prognosis; Trophoblastic Neoplasms; Uterine Neoplasms

A light microscopic analysis of lectin receptors in normal placenta and trophoblastic disease was performed utilizing biotinylated Concanavalin-A (Con-A), wheat germ agglutinin (WGA), and peanut agglutinin (PNA), in conjunction with an avidin-biotin peroxidase complex. Hydatidiform mole, invasive mole and choriocarcinoma exhibited increased receptors to Con-A and WGA compared to normal placenta. Increased reactivity to Con-A and WGA was associated merely with increased growth and proliferation of trophoblasts rather than a malignant transformation. Normal placenta, partial and complete mole generally showed moderate to strong binding with PNA after neuraminidase treatment, while invasive mole and choriocarcinoma (11 of 15 cases) generally showed minimal to absent reaction with PNA. Heterogeneity of PNA binding in choriocarcinoma was manifested by the presence of PNA reactivity in the trophoblast membrane in 2 cases wherein no prior neuraminidase treatment was given. This suggests that in some malignant trophoblasts, there is absence of sialic acid in the terminal cell surface carbohydrate groups resulting in the exposure of N-acetylgalactoseamine.

Topics: Choriocarcinoma; Concanavalin A; Female; Humans; Hydatidiform Mole; Hydatidiform Mole, Invasive; Lectins; Monosaccharides; Peanut Agglutinin; Placenta; Pregnancy; Trophoblastic Neoplasms; Uterine Neoplasms; Wheat Germ Agglutinins

We further studied the androgen-binding protein (ABP) that we recently evidenced in the serum from two patients with hydatidiform mole [Ref. 4]. This protein was further shown to be distinct from the sex hormone-binding globulin (SHBG) by concanavalin A and ion-exchange chromatographies, as well as spectrophotometric and kinetic studies. However, the ABP was shown to have a molecular weight and relative affinities for several steroids, similar to those of SHBG. Our results lead us to suppose that the ABP previously evidenced in molar vesicles and fluid [Ref. 5] is secreted in the serum. It is, however, likely that the secretion process alters the binding affinity of this protein. The presence of this additional binding component in the serum of patients with such trophoblastic tumours, may reduce severely the free 17 beta-hydroxyandrogens levels, as well as may help create a release gradient in the serum steroids buffer stores.

Topics: Androgen-Binding Protein; Carrier Proteins; Chromatography; Concanavalin A; Dihydrotestosterone; Female; Gonadal Steroid Hormones; Humans; Hydatidiform Mole; Pregnancy; Progesterone; Sex Hormone-Binding Globulin; Spectrophotometry; Uterine Neoplasms

Thyrotropic activity (TSH), measured by the McKenzie mouse bioassay, has been correlated with human chorionic gonadotropin (hCG) activity, measured by radioimmunoassay, in serum and tissue samples from 11 patients with hydatidiform mole and in partially and highly purified preparations of urinary hCG. Serum samples, taken at various times before and after removal of the moles, gave a ratio of 0.42 plus or minus 0.24 muU TSH/U hCG (mean plus or minus SD) (N)=43). In all cases where hCG activity fell below 150-175 U/ml (n=49), thyroid stimulating activity was undetectable (smaller than 40 muU/ml). We extracted lyophylized molar tissue by a modification of the Bates alcohol-saline method and purified the resultant extract by a combination of gel chromatography, affinity chromatography using Concanavalin A coupled to Sepharose, and isoelectrofocusing. Following extraction, an approximately 20-fold purification was achieved without significant alteration of the ratio of the two activities. Using results from all phases of purification the ratio of muU TSH/U hCG was 0.51 plus or minus 0.35(n = 23). Both activities were in the same position on disc gel electrophoresis. Activity ratios were less constant when partially purified preparations of urinary hCG were assayed for both thyrotropic and hCG activities. The presence of an hCG immunoreactive species, presumably hCG-beta subunit, which contains no thyrotropic activity but has an approximately 10-fold greater activity on a weight basis than intact hCG, may be a partial explanation for this observation. Isoelectrofocusing of a urinary hCG preparation showed that all hCG immunoreactive species with pl's between 3. 5 and 5.0 contained thyrotropic activity in proportion to their hCG content. Seven highly purified hCG preparations had thyrotropic activity with a ratio of 0.48 plus or minus 0.18 muU TSH/U hCG. These results indicate that hCG has intrinsic thyrotropic activity. On a molecular basis it is calculated that hCG contains approximately 1/4000 the thyrotropic activity of human pituitary TSH. In conditions of grossly elevated serum hCG levels, such as hydatidiform mole, this thyrotropic activity can be sufficient to produce hyperthyroidism.

Topics: Biological Assay; Chorionic Gonadotropin; Chromatography, Affinity; Chromatography, Gel; Concanavalin A; Electrophoresis, Disc; Female; Humans; Hydatidiform Mole; Isoelectric Focusing; Pregnancy; Radioimmunoassay; Thyrotropin