Sylvain Meuris

Serum levels of intact human chorionic gonadotropin (HCG) and its free a and β subunits, in relation to maternal thyroid stimulation during normal pregnancy

The main objective of the present study was to present additional evidence of the potentially important thyrotropic role of hCG to regulate the maternal thyroid gland during normal pregnancy. Sequential determinations (first and last trimesters) of intact hCG, free α and β-hCG subunits concentrations (using monoclonal IRMAs), and assessment of parameters of thyroid function and thyroid volume were carried out in 62 pregnant women who exhibited during the first trimester of gestation low TSH levels (≤0.20 mU/L), and compared to 276 pregnant women with normal TSH levels. The prevalence of having low serum TSH represented 18% of all pregnancies, with almost one half of cases who transiently had undetectable TSH levels. Lowering of TSH was associated with high hCG levels, and occurred primarily during the first trimester. About 10% of women with low TSH presented transient gestational thyrotoxicosis, frequently associated with vomiting. In comparison to control subjects, women with a suppressed serum TSH had significantly and markedly higher intact hCG and free β-hCG subunit concentrations. The results suggest that TSH reduction may result from a relative oversecretion of both intact hCG and free β-hCG subunits, compatible with three hypotheses: a) transient overexpression of the β-hCG gene, leading to enhanced production of hCG heterodimer; b) increased glycosylation of circulating hCG, with in turn a prolonged half life; c) larger syncytiotrophoblast mass with increased hCG production. Increased hCG in women with low TSH was clearly associated with thyroidal stimulation: comparing women with or without low TSH, it was shown that high hCG production was accompanied during the first trimester by a 20% mean increase in free T4 levels and a parallel increase in the TBG saturation levels by T4. Furthermore, thyroidal stimulation during the first trimester was associated with a larger median thyroid volume. During the last trimester and at term, most parameters of thyroid function were similar in both groups. In conclusion, a partial or total serum TSH suppression is a frequent finding during normal pregnancy, usually occurring as a transient feature near the end of the first trimester, in association with high serum hCG levels. The present data indicate for the first time that in these women, circulating hCG is characterized by elevated free β-hCG subunit and intact hCG levels, perhaps resulting from an imbalanced production of hCG. In approximately one percent of pregnancies, excessive thyroidal stimulation may lead to gestational transient thyrotoxicosis during the first trimester. The present studies confirm the role of hCG as an important thyroidal regulator during normal pregnancy.

The thyrotrophic role of human chorionic gonadotrophin (hCG) in the early stages of twin (versus single) pregnancies.

Human chorionic gonadotrophin (hCG) is known to possess thyroid‐stimulating activity. The aim of the present study was to assess the role of hCG in stimulating the maternal thyroid gland in the early stages of normal gestation.

Rapid electrotransfer of proteins from polyacrylamide gel to nitrocellulose membrane using surface-conductive glass as anode

A new type of inexpensive horizontal apparatus for the electrophoretic transfer of proteins from a gel to an immobilization membrane has been developed. In this system, gel and membrane were directly pressed between two flat electrodes. A surface-conductive glass was used as anode and a stainless-steel plate as cathode. Proteins could be transferred from polyacrylamide gel to nitrocellulose sheet, with a yield of at least 90% in 60-90 min, without overheating, using a voltage gradient of 30-40 V/cm. Moderate volumes of separate anodic (with 20% methanol) and cathodic (with 0.1% sodium dodecyl sulfate) buffers were suited for optimal transfer of proteins with relative molecular mass (Mr) in the 14,000-94,000 range.

Evidence for a clathrin-mediated recycling of albumin in human term placenta.

Abstract During human pregnancy, the trophoblast layer is in direct contact with maternal albumin. In contrast to immunoglobulins, albumin does not cross the placental barrier. However, albumin affects the trophoblast placental lactogen and chorionic gonadotroph secretion. The present study investigated the interaction between albumin and syncytiotrophoblast using human term placental explants. Bovine serum albumin, labeled with either 125I or fluorescein isothio-cyanate, was taken up rapidly by placental explants. This process was temperature-sensitive. The internalized labeled BSA quickly outflowed from the tissue at the maternal side, largely without any major modification in molecular weight. Colchicine (1 mM), which disrupts the microtubule network, or cytochalasin B (40 μM), which disassembles filamentous actin, did not interfere with the placental transmembrane movements of labeled BSA. Megalin, clathrin, and caveolin 1 are three membrane proteins associated with albumin endocytosis in other tissues, but only megalin and clathrin were detected in the syncytiotrophoblast layer by immunohistochemistry. The uptake of labeled BSA into placental explants was not modified by 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (1 mM) or 5-nitro-2-(3-phenylpropylamino)benzoic acid (100 μM), two pharmacological tools known to disturb megalin-mediated albumin endocytosis. By contrast, methyl-β-cyclodextrin (10 mM) and chlorpromazine (1.4 mM), both of which disrupt the clathrin-mediated endocytotic system, significantly reduced the uptake of labeled BSA. These data suggest, to our knowledge for the first time, that maternal albumin is actively internalized into the human trophoblast according to an apical recycling pathway. This temperature-sensitive process does not depend on an intact cytoskeleton, but it is associated with a clathrin-mediated endocytotic system.

Maternal height and external pelvimetry to predict cephalopelvic disproportion in nulliparous African women: a cohort study

Objective To assess external pelvimetry and maternal height, as predictors of cephalopelvic disproportion.

Maternal serum testing for alpha-fetoprotein and human chorionic gonadotropin in high-risk pregnancies

To evaluate the variations and potential clinical use of serial maternal alpha‐fetoprotein (AFP) and human chorionic gonadotropin (hCG) in pregnancies at risk of pregnancy‐induced hypertension (PIH) and/or intrauterine growth retardation (IUGR), we investigated the relationship between placental sonographic findings, uterine artery Doppler measurements, and maternal serum AFP, hCG, and uric acid levels between 20 and 34 weeks of pregnancy. Maternal serum samples were collected from 41 singleton pregnancies with bilateral uterine notches and/or an increased uterine artery pulsatility index at 20–24 weeks. Maternal serum AFP, intact hCG and free α and β subunits, and uric acid circulating levels were measured in all cases at 20–24 weeks and 25–28 weeks. Placental sonographic investigations comprised measurements of thickness and morphology. Twenty pregnancies had a normal outcome and 21 had an adverse outcome, including eight complicated by severe PIH with fetal IUGR, eight by isolated IUGR, three by mild PIH with normal fetal growth, and two by placental abruption. At the time of the first scan, the placental thickness and maternal serum levels of AFP, hCG, and uric acid were significantly increased in pregnancies with adverse outcomes, compared with those with a normal outcome. In subsequent maternal serum examinations, the incidence of elevated hormonal levels fell for AFP, intact hCG, and β‐hCG, whereas it increased for the uric acid level. No difference was found at any stage for the α‐hCG level. Seven out of 11 pregnancies complicated by PIH presented with elevated MSAFP and MShCG and a large heterogeneous placenta at the first visit, whereas no pregnancy with a normal outcome presented with similar features. This study has shown a significant association between abnormal development of the utero‐placental circulation, elevated MSAFP and MShCG at mid‐gestation, and subsequent adverse pregnancy outcome. Serial measurements of MSAFP and MShCG do not provide extra information for the follow‐up of these pregnancies.

Ca2+ entry through L-type voltage-sensitive Ca2+ channels stimulates the release of human chorionic gonadotrophin and placental lactogen by placental explants

The release of human chorionic gonadotrophin (hCG) and placental lactogen (hPL) by human placental explants can be stimulated by Ca2+ entry. The aim of the present study was to characterize the modality of Ca2+ entry in the presence of high extracellular K+ concentration ([K+]o). A rise in [K+]o from 5 to > or = 50 mM induced a rapid and marked increase in the release of hCG and hPL from human term placental explants. The stimulatory effects of an excess [K+]o on the release of hCG and hPL were blocked in the absence of extracellular Ca2+ or in the presence of 0.5 mM Co2+. The presence of 50 microM methoxyverapamil, 20 microM nifedipine or 40 microM Cd2+ in the medium inhibited the stimulatory effects of [K+]o addition. Lastly, 40 microM Ni2+ failed to affect the increases in hCG and hPL releases elicited by [K+]o addition. Our data clearly show that a rise in [K+]o stimulates the release of hCG and hPL from placental explants. These secretory effects can be viewed as resulting from a Ca2+ entry through voltage-sensitive Ca2+ channels of the L-type.

Immunoenzymatic localization of prolactin-like immunoreactivity in decidual cells of the endometrium from pregnant and nonpregnant women

Prolactin-like immunoreactivity has been localized by an immunoenzymatic method in the decidual cells of the endometrium in cases of early (10 weeks) normal pregnancy, (12 weeks) molar pregnancy, (8--10 weeks) tubal pregnancy, and of a nonpregnant woman under progestogen (lynestrenol) treatment. A specific endocrine influence, predominantly progestogenic, rather than the implantation of trophoblastic tissue seems to be required for the appearance of prolactin-like immunoreactivity in the decidual cells of the endometrium.

Chorangiocarcinoma: An unusual tumour of the placenta. The missing link?

A tumour occurring in an otherwise normal placenta presented the vascularity of a mature chorangioma but was surrounded by a neoplastic trophoblastic proliferation. A chorangioma with an atypical associated trophoblastic proliferation has never been reported in any of nearly 500 cases of chorangiomas described in the literature. The possibility of a combined lesion (for which we propose the term chorangiocarcinoma) is emphasized. It cannot be excluded however that chorangiomas could be, in rare cases, true neoplasms rather than hamartomas.

Monomeric pituitary growth hormone and prolactin variants in man characterized by immunoperoxidase electrophoresis

Immunoperoxidase electrophoresis, combining SDS‐ME‐PAGE and the ‘double bridge’ immunoperoxidase staining was applied to crude human pituitary homogenates. With anti‐hGH and anti‐hPL sera, 4 hGH‐related monomers were characterized: a M r 22 000 peptide corresponding to hGH; a M r 20 000 peptide corresponding to the known hGH variant and two unknown hGH variants (M r 65 000 and M r 75 000). With anti‐ovine, rat and human PRL sera, 4 PRL‐related monomers were immunostained: one comigrated with purified hPRL (M r 25 000), and 3 were unknown (M r 29 000; M r 45 000; M r 16 000).