The maternal and fetal levels of human chorionic gonadotropin, human placental lactogen and prolactin during the perinatal period (author's transl)

The levels of human chorionic gonadotropin (HCG), human placental lactogen (human choriosomatomamotropin HCS) and prolactin (PRL) were determined in the serum of 72 maternity patients and the serum of the newborn infants. The determinations were done with radioimmunologic tests (RIA). These three protein hormones were also determined in the amniotic fluid and in the maternal serum from 4-6 days prior to the delivery of the infant. The concentration of HCG or HCS in the serum of the newborn infants was a mean 0.43 or 0.37% of the level in the maternal serum. The concentration of PRL in the serum of the newborn was 118% and slightly higher than in the serum of the mothers. The concentration in the amniotic fluid was 1.5% for HCG, 5.8% for HCS, and 252% for PRL, compared to the corresponding levels in the maternal serum. The fact that the hormone concentrations in the amniotic fluid are significantly higher than in the serum of the newborn suggests excretion of the hormones from the fetal circulation via the fetal liver and the fetal kidney. The high levels of PRL in the maternal and the newborn serum may be caused by the high concentrations of estrogen or progesterone. Increased during the course of the pregnancy there was a significant sex linked difference in the level of HCG in the maternal serum correlated to the sex of the newborn infant.     

Urinary oestrogen and plasma human placental lactogen as initial screening tests for a placental sulphatase deficiency

As a result of routine screening of ante-natal patients by urinary total oestrogens and plasma human placental lactogen (HPL) from 35 weeks, a rare placental sulphatase deficiency was indicated which was later confirmed by in vitro studies of placental enzyme activities.     

Ovine placental lactogen induces somatomedin: a a possible role in fetal growth

Ovine placental lactogen (oPL) and bovine growth hormone (bGH) increase the circulating concentration of somatomedin in hypophysectomized rats. This finding indicates that some of the somatotropic properties of oPL may be due to the induction of somatomedin and raises the possibility that oPL has a role in the control of fetal growth.     

Placental site trophoblastic tumor: human placental lactogen and pregnancy-associated major basic protein as immunohistologic markers

Placental site trophoblastic tumor (PSTT) consists of a neoplastic proliferation of intermediate or extravillous trophoblast (also known as X cells). Pregnancy-associated major basic protein (pMBP) is a marker for placental intermediate trophoblast. We compared the distribution of pMBP and human placental lactogen (hPL) in 24 PSTT and 3 exaggerated placental site (EPS) specimens using two distinct immunohistologic methods. Statistical analyses were used to compare staining intensities in metastatic and nonmetastatic lesions. By immunofluorescence, 77% of the PSTT specimens and 100% of the EPS specimens stained with antibodies to pMBP, and the pMBP was localized in intermediate trophoblast and surrounding extracellular areas. By immunohistochemistry, 78% of the PSTT specimens and 100% of the EPS specimens stained for pMBP with a pattern comparable with that of immunofluorescence. Likewise, by immunohistochemistry, hPL stained 96% of the PSTT specimens and 100% of the EPS specimens. Immunohistochemical staining intensities for pMBP and hPL correlated (r2 = +.24; P = .013), but hPL staining was mainly confined to intermediate trophoblast and was more intense. Anti-pMBP tended to stain metastatic PSTT weakly. Thus, pMBP is a useful marker for intermediate trophoblast tumors and could help distinguish these from other forms of trophoblastic disease.     

Ineffectiveness of human chorionic gonadotropin in weight reduction: a double-blind study

Our investigation was designed to retest the hypothesis of the efficacy of human chorionic gonadotropin (HCG) on weight reduction in obese women in a clinic setting. We sought to duplicate the Asher-Harper study (1973) which had found that the combination of 500 cal diet and HCG had a statistically significant benefit over the diet and placebo combination as evidenced by greater weight loss and decrease in hunger. Fifty-one women between the ages of 18 and 60 participated in our 32-day prospective, randomized, double-blind comparison of HCG versus placebo. Each patient was given the same diet (the one prescribed in the Asher-Harper study), was weighed daily Monday through Saturday and was counselled by one of the investigators who administered the injections. Laboratory studies were performed at the time of initial physical examinations and at the end of the study. Twenty of 25 in the HCG and 21 of 26 patients in the placebo groups completed 28 injections. There was no statistically significant difference in the means of the two groups in number of injections received, weight loss, percent of weight loss, hip and waist circumference, weight loss per injections, or in hunger ratings. HCG does not appear to enhance the effectiveness of a rigidly imposed regimen for weight reduction.     

The lecithin/spingomyelin quotient as determined using a modified method and human placental lactogen in the amniotic fluid

Thirty amniotic fluid samples in late gestational age were analysed for HPL-values and the L/S-ratio. The pregnant women used in this study were healthy except three patients who developed a rh-incompatibility. The amniotic fluid was only obtained by abdominal amniocentesis. We found a decreasing tendency of the HPL-values in late pregnancy. The L/S-ratio increased. A significant correlation of both values could not be observed. In all three cases of rh-incompatibility the decrease of HPL and the increase of the L/S-ratio occurred obviously earlier and steeper. Further studies will prove the significance of these results.     

Assessment of urinary beta-core fragment of human chorionic gonadotropin as a new tumor marker of lung cancer

BACKGROUND: Some patients with lung cancer have been found to have elevated levels of serum immunoreactive human chorionic gonadotropin (hCG)/hCG beta (IR-beta), but it is uncertain whether it would be valuable as a tumor marker. Recently, IR-beta has been demonstrated to consist of at least three different molecules, intact hCG, free hCG beta, and hCG beta-core fragment (beta-CF), in body fluids. In this study, the authors qualitatively analyzed IR-beta in the serum and urine of patients with lung cancer and assessed its clinical usefulness as a tumor marker. METHODS: Highly sensitive and specific enzyme immunoassays were established to measure intact hCG, free hCG beta, and beta-CF in the serum and urine of patients with lung cancer. RESULTS: Of 99 patients with lung cancer, almost half of the patients achieved positive values of IR-beta in the urine, although only 12 had elevated values of IR-beta in the serum. The greater part of the elevated urinary IR-beta was identified to be beta-CF by gel chromatography on Sephadex G-100 (Pharmacia LKB Biotechnology, Tokyo, Japan), leading the authors to assess its usefulness as a tumor marker for lung cancer. Based on the cutoff value (0.2 ng/mg of creatinine) from healthy subjects, the overall positive rate of urinary beta-CF for lung cancer was 48.5% (48 of 99 patients). The incidence of the marker increased with stage of disease, from 35.7% (15 of 42) in Stage I and 35.7% (5 of 14) in Stage II to 62.5% (20 of 32) in Stage III and 72.7% (8 of 11) in Stage IV. These positive rates exceeded or equaled those of the serum tumor markers, carcinoembryonic antigen, and squamous cell carcinoma (SCC)-related antigen, measured simultaneously in the same patients. The author were encouraged that there was no significant difference in the positive rates of urinary beta-CF between two major types of lung cancer: adenocarcinoma (49.2%) and SCC (45.2%). Immunohistochemical study revealed positive staining of IR-beta in the cancer tissues from 5 of 12 patients with elevated levels of IR-beta, in which most of the positive cases had the elevated levels of serum free hCG beta (> 0.5 ng/ml) and/or urinary beta-CF (> 1.0 ng/mg of creatinine). CONCLUSIONS: Ectopic production of IR-beta by lung cancer is not rare, and urinary beta-CF might be a potential tumor marker of lung cancer.     

Immunoprocedures for detecting human chorionic gonadotropin: clinical aspects and doping control

The pregnancy hormone human chorionic gonadotropin (hCG) is also present at low concentrations in plasma and urine of men and nonpregnant women. hCG immunoreactivity occurs in various molecular forms: Besides the intact hCG heterodimer, considerable amounts of proteolytically cleaved forms, free subunits, and fragments are found in plasma and urine. Especially in urine, proteolytic fragments constitute a major part of the hCG immunoreactivity. The different forms of hCG cross-react to various degrees in immunoassays and constitute a problem for standardization of specific hCG determinations. After injection of hCG (10,000 IU of Pregnyl; Organon), above-normal concentrations of hCG can be detected in serum and urine for 7-11 days. Most immunoassays for hCG also measure hCG beta. Quantitative hCG determinations are mainly performed on serum samples, and very few commercial hCG determinations have been validated for determination of urine samples. Considerable care must therefore be exercised when utilizing such assays to analyze urines for doping control.     

Immunoperoxidase localisation of human placental lactogen: a marker for the placental origin of the giant cells in ''syncytial endometritis'' of pregnancy

Various common C4 gene products were isolated from serum by immunoprecipitation. After reduction the C4 alpha-, beta-, and gamma-polypeptide chains were studied by two-dimensional electrophoresis. Isoelectrofocusing was performed in the first dimension and sodium dodecyl sulphate polyacrylamide gradient gel electrophoresis in the second. The charge differences behind the electrophoretic C4 polymorphism were shown to reside in the 95,000-u (atomic mass units) alpha-chain. Charge variation closely mirroring the alpha-chain differences were also found in a 49,000-u fragment of the alpha-chain, most probably C4d. The basic beta-chain could not be studied in detail, but no differences were observed with regard to molecular weight or charge of the gamma-chains of the different C4 gene products.     

Testing cord blood human chorionic gonadotropin as a surrogate marker for early identification of human immunodeficiency virus-1 infection in children

We measured human chorionic gonadotropin (hCG) in cord sera of 22 infants born to women infected with the human immunodeficiency virus-1 (HIV-1). hCG was also determined in cord sera from 173 infants born at a suburban hospital to HIV-1-seronegative women. The findings indicate that 16 (9%) of 173 HIV-1-seronegative samples had hCG levels greater than 90 IU/L (values were distributed as a Poisson curve). In contrast, 8 (36%) of the 22 infants born to HIV-1-infected women had hCG levels in excess of 90 IU/L, and 7 (88%) of these were shown to be HIV-infected. The remaining 14 infants born to HIV-1-infected women had low hCG levels, and 3 (21%) of the 14 had HIV infection. Mean follow-up time for HIV-uninfected infants was 17.5 months (range 9 months to 3 years). A statistically significant association between maternal-fetal HIV-1 transmission and hCG levels > or = 90 IU/L in cord sera was observed (p = 0.02). The difference between CD4 counts among mothers who transmitted HIV and those who did not was also statistically significant (p = 0.025). On the basis of this study's findings, we propose that cord blood hCG may serve as a surrogate marker for HIV-1 infection. Testing hCG levels in cord sera is an inexpensive and readily available screening test for early identification of infants at increased risk for getting HIV-1 from their mothers.     

Choriocarcinoma with hyperthyroidism: probable identity of the thyrotropin with human chorionic gonadotropin

A 15-year-old girl developed severe hyperthyroidism secondary to metastatic choriocarcinoma. Her serum contained high levels of human chorionic gonadotropin (HCG) by radioimmunoassay and had a thyroid-stimulating activity different from that of pituitary thyrotropin (TSH) or of long-acting thyroid stimulator (LATS) in the McKenzie mouse bio-assay. Gradient ultracentrifugation localized this thyroid stimulator to a narrow zone midway between markers of transferrin and ovalbumin. On gel filtration it emerged just before albumin as a single peak coinciding with the peak for HCG. Her HCG was identical to an authentic sample of HCG in position to gel filtration columns and on gel electrophoresis. These results suggest that the thyrotropin of choriocarcinoma is HCG.     

Follicle stimulating activity of human chorionic gonadotropin: effect of dissociation and recombination of subunits

The follicle stimulating activity (FSA) and interstitial cell stimulating activity (ICSA) of highly purified human chorionic gonadotropin (hCG), its alpha and beta subunits, and hCG generated by subunit recombination were determined by ovarian weight and ventral prostate weight bioassays. Whereas highly purified hCG exhibited both FA and ICSA, its separated subunits were essentially devoid of both activities. ICSA and FSA, indistinguishable from that of the highly purified hCG, were restored by recombination of the hCG subunits. These observations are consistent with the hypothesis that the FSA and ICSA found in highly purified hCG preparations are properties of the hCG molecule.     

Postoperative day 1 serum human chorionic gonadotropin level as a predictor of persistent ectopic pregnancy after conservative surgical management

OBJECTIVE: To determine characteristics predictive of persistent ectopic pregnancy (EP). DESIGN: Retrospective cohort study. SETTING: Tertiary care, university hospital. PATIENT(S): All women treated surgically for an EP whose postoperative hCG levels were followed until complete resolution or determination of a persistent EP over a 54-month period. MAIN OUTCOME MEASURE(S): Final outcome defined as successful treatment or persistent EP. RESULT(S): Twenty-six (17.7%) of 147 patients were diagnosed with a persistent EP. An inverse relationship was noted between the percent decrease in hCG at postoperative day 1 and the incidence of persistent EP. A significantly greater percentage of persistent EPs were noted when the postoperative day 1 hCG fell < 50% from the initial preoperative hCG level (relative risk = 3.51 [1.25 to 6.68]). No case of persistent EP was noted if the postoperative day 1 hCG declined by > or = 77%. Surgical time differed significantly (129 minutes versus 101 minutes) between cases treated successfully as compared with cases in which conservative treatment failed. No other preoperative or intraoperative variables were found to be significantly different. CONCLUSION(S): Although no single postoperative hCG value is predictive of conservative surgical treatment for EP, a day-1 postoperative hCG value may be used as a predictor of persistent EP.     

Crucial role of serum human chorionic gonadotropin for the aggravation of thyrotoxicosis in early pregnancy in Graves' disease

Thyrotoxicosis in Graves' disease is often aggravated in early pregnancy and is closely associated with postpartum recurrence of stimulative thyrotoxicosis. To examine whether thyroid-stimulating TSH receptor antibody (TSAb) or human chorionic gonadotropin (hCG), which also has thyroid-stimulating activity (TSA), was responsible for this early aggravation, the respective TSA due to TSAb or hCG was evaluated by a highly sensitive cAMP accumulation assay using FRTL-5 cells. TSA was detectable in all of 11 women in normal early pregnancy, correlated positively with serum hCG concentration, and was abolished completely by the pretreatment of serum sample with the solid-phase hCG antibody coupled with Sepharose 4B. The model serum samples of Graves' disease with pregnancy were made by the mixture of normal pregnant and Graves' sera, and their TSA were reduced by the pretreatment with the solid-phase hCG antibody, just corresponding with the reduction in hCG-induced TSA. TSA of early pregnant sera in 20 patients with Graves' disease decreased significantly but were still positive even after the pretreatment with the hCG antibody. Serial changes in TSAb and hCG-induced TSA were measured in 5 of these 20 pregnant patients. hCG-induced TSA increased associated with the increase in free thyroxine, while TSAb did not show striking change in early pregnancy. These data indicate that (1) respective TSA due to TSAb or hCG can be measured distinctively by using the solid-phase hCG antibody and (2) hCG plays a crucial role in the aggravation of Graves' thyrotoxicosis in early pregnancy.     

The intracerebroventricular injection of interleukin-1beta blunts the testosterone response to human chorionic gonadotropin: role of prostaglandin- and adrenergic-dependent pathways

The present work extends our previous report that the intracerebroventricular (i.c.v.) injection of interleukin-1beta(IL-1beta, 80 ng) significantly blunted the testosterone response to 1 U/kg human CG (hCG), an effect that we attributed to the stimulation of inhibitory pathways connecting the hypothalamus to the testes. Systemic blockade of prostaglandin-dependent pathways with ibuprofen (alpha-methyl-4-[2-methylpropyl]benzeneacetic acid; sodium salt), which did not, in itself, alter the stimulatory effect of hCG on testosterone release in control rats, modestly, but significantly (P < 0.05) reversed the inhibitory influence of IL-1beta. In contrast, blockade of brain receptors for CRF was unable to alter the effect of IL-1beta, as were lesions of the ventromedial hypothalamic nucleus, a brain area implicated in the control of ovarian function. Blockade of beta-adrenergic receptors significantly prevented the decrease in testicular responsiveness induced by the i.c.v. injection of IL-1beta. Finally, the central injection of the beta-adrenergic agonist isoproterenol, as well as that of norepinephrine, mimicked the ability of icv IL-1beta to blunt testicular secretory activity and produced a marked (P < 0.01) decrease in the response to hCG within 5 min of their administration. We propose that the explanation that best fits our findings is that the i.c.v. injection of IL-1beta activates a neural, catecholamine-dependent pathway that connects the brain and the testes independently of the pituitary.     

Plasma levels of oestriol-17 beta, oestriol and human placental lactogen during bed rest

Plasma unconjugated oestradiol-17 beta, total oestriol and human placental lactogen levels were measured in twelve healthy volunteers admitted for bed rest in the last trimester of pregnancy. No significant alteration in levels was observed.     

Disulfide bonds 7-31 and 59-87 of the alpha-subunit play a different role in assembly of human chorionic gonadotropin and lutropin

CG, LH, FSH, and TSH are a family of heterodimeric glycoprotein hormones that contain a common alpha-subunit but differ in their hormone-specific beta-subunits. Both subunits have five and six disulfide bonds, respectively, which consists of cystine knot structure. We previously eliminated the disulfide bonds 7-31 and 59-87 in alpha-subunit without significantly affecting assembly with human CG beta-subunit. To study the role of these disulfide bonds in dimerization with other beta-subunits, the wild-type or mutated alpha gene was contransfected with the wild-type human LH beta or FSH beta gene into Chinese hamster ovary (CHO) cells or GH3 cells, and assembly was assessed by continuous labeling with [35S]methionine/cysteine, immunoprecipitation with anti-alpha or-beta serum, and SDS-PAGE. Our data revealed that disruption of either disulfide bond 7-31 or 59-87 in the alpha-subunit markedly reduced the dimer formation with LH beta-subunit in both CHO and GH3 cells, whereas it did not significantly affect the assembly of FSH. This suggests that the regions in the alpha-subunit recognized by beta-subunits for assembly are different among gonadotropins.     

Maternal thyroid function in multiple pregnancy: the variable thyrotropic activity of human chorionic gonadotropin

The present study was undertaken to evaluate thyroid function and thyrotropic action of hCG in multiple pregnancy. We examined serum samples from 9 multiple pregnant women (3 triplets and 6 twins) and 27 singleton pregnant women as control subjects. Serum hCG levels in multiple pregnancy were higher than those in singleton pregnancy in the second and third trimesters (P < 0.01). The mean free T3 and T4 concentrations in multiple pregnancy did not differ from those in singleton pregnancy in each trimester. Serum hCG levels showed a statistically significant positive correlation with free T3 and T4 levels in singleton pregnancy (P < 0.001). However, these correlations were not observed in multiple pregnancy. Thyroid stimulation activity (TSA) determined by cAMP accumulation in FRTL-5 cells in multiple pregnancy sera was significantly higher than that in singleton pregnancy in the first trimester (P < 0.05), but did not differ in the second and third trimesters. Moreover, TSA did not show any correlation with serum hCG levels in multiple pregnancy in contrast with the results in normal pregnancy. A bioactivity/immunoreactivity ratio of hCG in multiple pregnancy was lower than in singleton pregnancy in the second and third trimesters. The discrepancy between immunoreactivity and thyrotropic activity of hCG may be caused by the variable thyrotropic potency of heterogeneous hCG molecules in multiple pregnancy.