A chromatofocusing study of human chorionic gonadotropin in biological fluids in normal pregnancy, pre-eclampsia and choriocarcinoma.
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Biomedical subjects
Publications and source records attributed to C Y Hsieh.
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The study subjects included a total of 30 postmenopausal Chinese women, including 14 natural menopausal women, 13 castrated menopausal women and 3 post-irradiated menopausal women. Premarin 1.25 mg/day was given orally for 3 weeks and off one week, repeated for 6 cycles. Fasting morning urine and blood samples were collected before hormone treatment and at the end of 3 weeks, 11 weeks, and 23 weeks of Premarin therapy. Serum total estrogen level was measured by radioimmunoassay. Urinary calcium and creatinine were measured by atomic absorption and Jeffe's reaction, respectively. The concentration of urinary hydroxyproline was determined by Kivirikko's method. After Premarin therapy, the mean concentration of serum total estrogen increased 3 to 4 times from the pretreatment level of 71.7 pg/ml. On the other hand, the mean value of calcium/creatinine (Ca/Cr) molar ratio dropped down from 0.249 to 0.098. The mean value of hydroxyproline/creatinine (HOPr/Cr) molar ratio was reduced from 0.028 to 0.012. In view of the hormonal and biochemical changes after Premarin therapy, it is concluded that estrogen (Premarin) replacement should be effective in the treatment of enhanced bone loss or osteoporosis in postmenopausal women. The relationship of estrogen and calcitonin in the regulation of bone metabolism is also discussed.
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Monoclonal antibodies generated against human chorionic gonadotropin (hCG) were utilized in radio- and enzyme-immunoassays of this reproductive hormone in biological fluids. One of the monoclonal antibodies, beta-4D6, was shown to have extremely high affinity (Ka = 8 X 10(10) M-1)) and high specificity (less than or equal to 0.6% LH cross-reactivity) to beta-subunit of hCG and whole hCG. It was used in competitive radioimmunoassays (RIA) for the determination of low levels of serum hCG. An excellent correlation was obtained concerning the assay results between the monoclonal antibody-based system and others using conventional polyclonal anti-sera. In combination with another discrete hCG monoclonal antibody, solid-phase sandwich radiometric and enzyme immunoassays were established. These immunoassays could easily be performed, and they offer sensitivity and efficacy of hCG determination comparable to those of conventional ones.
Thirteen pregnancies in 11 women previously treated with cytotoxic chemotherapy for GTD were studied. There were 11 live full-term babies (84.6%), 2 blighted ova (15.4%), 1 placenta accreta (7.7%) and 1 fetal anomaly (7.7%). Unlike other series, 69% of the pregnancies occurred within 1 year after the termination of chemotherapy. The rate of successful pregnancy was not different from that reported by others. Prenatal elimination of abnormal embryos after conception rather than wastage of damaged oocyte before conception might explain this observed low incidence of abnormal birth in GTD patients treated with cytotoxic chemotherapy.
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alpha-Fetoprotein (alpha FP) and four placental proteins, human chorionic gonadotropin (hCG), human placental lactogen (hpL), pregnancy specific beta 1-glycoprotein (SP1), and placental protein 5 (PP5), were measured in a 17-year-old patient with endodermal sinus tumor of the ovary. The circulating levels of alpha FP were consistently high (more than 14 mg/ml), and alpha FP was localized in tissue sections using immunohistochemical techniques. None of the four placental proteins was detectable in serum samples, but hCG was detected in urinary concentrates in an episodic manner. This ectopic hCG resembled placental hCG in its physicochemical and immunological characteristics. Unlike alpha FP, hCG was not detected in the tumor by immunohistochemical methods. This study indicates that the neoplasm elaborated both hCG and alpha FP. Whether pure endodermal sinus tumor of the ovary is capable of secreting hCG cannot be answered by this study because of limited histologic sampling. The likelihood that this represents a mixed germ cell tumor in which only the endodermal sinus tumor element was sampled remains a possibility. This study also indicates that the 24-hr urinary concentrate is far more sensitive than serum samples for hCG detection.
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To study the secretion pattern of a hCG-like substance (hCG') in normal women and those employing contraceptive measures, we assayed daily urine concentrates by RIAs using an anti-hCG beta-COOH-peptide serum and an anti-hCG serum to monitor hCG' and human LH (hLH), respectively. In eight cycles of four normal women, urinary hCG' was within the normal range (less than 100 ng/day), except that four samples in two women had marginal elevations of hCG' during the menstrual or premenstrual period, but not at the time of the midcycle hLH surge. Among seven cycles from three intrauterine device (IUD) users, six showed midcycle hLH surges, and in five, hCG' was prominent (0.17-3.6 micrograms/day) in the late luteal phase. In eight cycles of women ingesting steroid contraceptives on a conventional schedule, hCG' was found during the premenstrual and menstrual intervals. The pattern of hCG' secretion was episodic, and hCG' levels were in the range of 0.3-1.8 microgram/day. It was notable that hCG' was excreted at the highest levels during intervals when ingestion of steroids was withheld. These findings suggest that contraceptive steroid hormones may modulate pituitary hCG' secretion. From gel high pressure liquid chromatographic studies, the immunoactive hCG' detected in urinary extracts from normally cycling women and IUD users had a molecular size larger than hCG beta and hLH, but was slightly smaller than hCG (lot CR119). The hCG' identified in these eluents is unlikely to be a subunit of hCG. On the other hand, the immunoactive hCG' in the urinary extracts from oral contraceptive users was mainly the hCG beta-subunit-like substance. Both hCG alpha and hCG beta immunoactive substances were heterogeneous in size in contrast to those found in normally cycling women and IUD users. In summary, the hCG' excretion pattern was different in menstrual and postmenopausal women, and hCG' identified in these subjects was heterogeneous.
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The concentrations of catecholamines in cord venous plasma were measured by trihydroxyindole fluorimetric assay in four fetuses with normal fetal heart rate (FHR) and three distressed fetuses with late deceleration of pathologic FHR. The concentrations (nmol/l) of norepinephrine and epinephrine in normal fetuses were 40.3 +/- 7.9 (mean +/- SD) and 5.4 +/- 1.5, respectively, whereas those in distressed fetuses were 156.8 +/- 48.0 and 12.1 +/- 4.5, respectively. In normal fetuses about 88% of total catecholamines consisted of norepinephrine, the remaining 12%, epinephrine. The ratio of norepinephrine to epinephrine in distressed fetuses (12.9) was thus higher than the ratio in normal fetuses (7.5). Higher levels of total catecholamine concentrations were associated with the presence of late deceleration of pathologic FHR pattern, low one-minute Apgar score, low umbilical arterial pH value (pH less than 7.20), and fetal hypertriglyceridemia (greater than 48 mg/100 ml). The relationship between fetal hypertriglyceridemia and elevated concentration of cord plasma total catecholamines is elucidated and the physiologic significance of increased secretion of catecholamines in distressed fetuses is discussed.