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Peritoneal dialysis with 5% glucose solution was carried out in dexamethasone-pretreated rats. Dialysis brought about a severe loss of sodium and a slight loss of potassium into the peritoneal fluid. This kind of sodium depletion took place without any decrease in total body-water space, thus it evoked a severe fall in plasma sodium concentration.

Plasma renin activity and the serum concentration of aldosterone increased in response to dialysis. Peak values in renin activity were attained within 60 min, whereas aldosterone concentrations exhibited a continuous rise until at least 120 min. Despite the correlation of renin and aldosterone values, neither the administration of an angiotensin I converting enzyme inhibitor (SQ 20,881) nor the reduction of plasma renin activity by indomethacin could reduce hyperaldosteronism evoked by peritoneal dialysis. Therefore, it is assumed that there is no causal relationship between renin and aldosterone in this kind of acute, severe sodium depletion.

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Alloxan-diabetic rats produce significantly less granulation tissue than normal ones. Locally applied growth hormone (STH), which stimulates granulation tissue in normal rats, lost this ability in diabetic animals. Adrenalectomized alloxan-diabetic rats also fail to respond by increased granulation tissue growth to STH. The stimulation of granulation tissue by STH seems to depend on an adequate supply of insulin.

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A-M Nagy, E Jauniaux, D Jurkovic, and S Meuris


Levels of human chorionic gonadotrophin (hCG) and of its free α and β subunits were measured using specific immunoradiometric assays in exocoelomic fluid (ECF) and maternal serum (MS) collected from five pregnant women at 6·6-8 weeks of gestation. Mean levels of hCG and its free subunits were significantly (P<0·001) higher in ECF than in MS: 3·5-fold for hCG, 600-fold for free αhCG and 38-fold for βhCG. There was no correlation between either hCG levels or levels of its free subunits in ECF and MS. On a molar basis, the quantity of free αhCG subunit expressed as a percentage of the total (free+combined) amount was 83% in ECF and 2·7% in MS (P<0·001). The amount of free βhCG subunit as a percentage of the total was 22% in ECF and 3·5% in MS (P<0·001). The ratio of the total amounts of α- and βhCG subunits amounted to 4·6 in ECF and 0·99 in MS (P<0·001).

The heterogeneity of hCG was further investigated by polyacrylamide gel electrophoresis followed by immunoblotting. Several bands with molecular mass ranging from 42 to 57 kDa, corresponding to hCG dimers, were immunodetected in ECF and MS with anti-αhCG and anti-βhCG monoclonal antibodies. A free 35 kDa βhCG immunoreactive band was found in ECF and MS. A free αhCG immunoreactive band was observed at 23 kDa in ECF and at 21 kDa in MS.

These findings suggest that the exocoelomic cavity is a reservoir where hCG and its subunits produced by trophoblast accumulate directly. The excess of a free heavy αhCG subunit in ECF supports the hypothesis that, during early pregnancy, there is an excess of αhCG over βhCG subunit secretion by the trophoblast.

Journal of Endocrinology (1994) 142, 511–516

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The present experiments were designed to study the effect of extracellular hyponatraemia on aldosterone secretion. Hyperaldosteronism was induced by peritoneal dialysis with 5% glucose solution in dexamethasone-pretreated rats. In the narrow physiological range of 135–142 mmol/l, as well as in the whole range of the study (122–142 mmol/l), the plasma concentration of sodium showed a close negative correlation with the serum concentration of aldosterone (r = −0·71 and −0·83, respectively). Plasma renin activity increased after peritoneal dialysis; however, no close correlation was observed either between sodium concentration and plasma renin activity or plasma renin activity and serum aldosterone concentration within the dialysed group. The ratio of serum concentration of aldosterone to plasma renin activity showed no considerable change between 132 and 142 mmol/l but rose steeply below 132 mmol sodium/l suggesting that a factor(s) other than angiotensin may also contribute to the induction of hyperaldosteronism.

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E Jauniaux, K H Nicolaides, A-M Nagy, M Brizot, and S Meuris


The aim of this study was to evaluate the variations in the balance between total (free and combined) circulating α and β subunits of human chorionic gonadotrophin (hCG) in trisomy 21 and 18.

Maternal serum samples were collected at 10 and 11 weeks of gestation from 22 singleton pregnancies with trisomy 21 (n=17) and trisomy 18 (n=5) and 66 chromosomally normal controls, matched for gestational age. The hCG and free α and β subunits circulating levels were measured using specific immunoradiometric assays and converted in a common unit system obtained using calibration of the assays with intact and thermally dissociated purified hCG preparation.

In trisomy 21, the only significant difference from controls was in the free βhCG level which was increased. In trisomy 18, intact hCG, free βhCG as well as total αhCG and total βhCG levels were significantly lower whereas the free αhCG level was significantly higher than in controls. The decrease in total βhCG was more pronounced than the decrease in total αhCG resulting in a significant increase in the total α- to βhCG subunit ratio in trisomy 18.

These findings suggest some modifications in the biosynthesis and/or release rates of the hCG subunits in these trisomies.

Journal of Endocrinology (1996) 148, 27–31

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E Mezosi, J Szabo, E V Nagy, A Borbely, E Varga, G Paragh, and Z Varga

Over the past few years increasing evidence has suggested the nongenomic effects of thyroid hormone, such as the activation of the signal transduction pathways and the activation of nuclear factor-κB by the induction of oxidative stress. The present study was undertaken to investigate the effect of thyroid hormone on human polymorphonuclear leukocytes (PMNLs) which are known as important sources of reactive oxygen species in the circulation. The production of superoxide anion (O2) and the activity of myeloperoxidase were determined in the presence and absence of several inhibitors of the signalling pathway. l-Thyroxine (T4) l-3,5,3′-tri-iodothyronine (T3) and l-3,5-di-iodothyronine (T2) stimulated O2 production in PMNLs in a dose-dependent manner within a few minutes of addition to cells. Thyroid hormone-stimulated O2 production was partially inhibited by pertussis toxin, an inhibitor of GTP-binding G protein, and was completely abolished by the protein kinase C inhibitors calphostin C and Ro-32–0432, and by a calcium chelator (BAPTA; bis-(o-aminophenoxy)ethane-N,N,N′,N′-tetra-acetic acid). Thyroid hormone stimulated myeloperoxidase activity and induced 125I incorporation into PMNLs. Furthermore, thyroid hormone pre-incubation enhanced O2 production for n-formyl-methionyl-leucyl- phenylalanine (FMLP) stimulation. In conclusion, novel nongenomic actions of thyroid hormone, the induction of superoxide anion production and the stimulation of myeloperoxidase activity in PMNLs were demonstrated. The induction of O2 production requires calcium and is mediated by a pertussis toxin-sensitive G protein via stimulation of protein kinase C(s). These results suggest the existence of a membrane-bound binding site for thyroid hormone in PMNLs and a physiological role for thyroid hormone in the cellular defence mechanisms by stimulating free-radical production.

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E Pap, K Racz, JK Kovacs, I Varga, E Buzas, B Madarasz, C Foldes, C Szalai, T Watanabe, H Ohtsu, A Ichikawa, A Nagy, and A Falus

Histamine is synthesized in cells by histidine decarboxylase (HDC). HDC-deficient knockout (KO) mice lack functional HDC and histamine in the tissues. In the present study we used this in vivo model for studying the role of HDC deficiency in the regulation of male steroid hormone metabolism. In agreement with earlier studies showing the lack of effects of central histamine on the basal secretion of gonadotrope hormones, we found no difference with in situ hybridization in the expression of GnRH in the hypothalamus of wild type and KO mice. The tissue concentrations of testosterone and several androgenic steroids were significantly elevated in the testes but not in the adrenal glands of HDC-KO mice. In contrast, serum estradiol levels failed to show a significant difference between the two groups. The weight of the testes was significantly smaller in both 7-day-old and adult KO mice. The ultrastructure of the adult testis indicated elevated steroid synthesis with more tightly coiled membranous whorls in Leydig cells. The present results suggest that changes in reproductive functions and sex steroid secretion in male HDC-KO mice are not due to altered hypothalamic GnRH expression but are probably related to definite modifications during fetal development of KO mice reinforced later by the lack of the effect of peripheral histamine. This may provide in vivo evidence that peripheral histamine is an important regulatory factor of male gonadal development during embryogenesis and of sex steroid metabolism later in adulthood.

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A-M Nagy, D Glinoer, G Picelli, J Delogne-Desnoeck, B Fleury, C Courte, J-M Kaufman, C Robyn, and S Meuris


The aim of the present study was to determine the variations in the balance between total (free plus combined) circulating α and β subunits of human chorionic gonadotrophin (hCG) throughout human pregnancy.

The equivalence between the International Units (IU) of hCG (IRP 75/537) and those assigned to the α (IRP 75/569) and β (IRP 75/551) free subunits was experimentally determined by using intact and thermally dissociated hCG. Heat exposure (2 min at 100 °C) of hCG preparations resulted in a complete dissociation of hCG into free, soluble and intact α and β subunits. The hCG and α and β subunit contents of unaltered and heated hCG preparations were assessed by specific immunoradiometric assays. The amount of immunoreactive subunits dissociated by heat from hCG could then be evaluated on a molar basis.

Circulating hCG and its free α and β subunits were immunoassayed in 836 blood samples collected from healthy pregnant women at different gestational ages. After conversion of hCG and its subunits into a common IU system, the gestational profiles of the total amounts (free plus combined) of α- and βhCG subunits increased together and peaked at 9–10 weeks of gestation. Thereafter, total α and β subunits decreased and subsequently remained stable until term. The decline in total αhCG subunit was less marked than that of total βhCG subunit. The α- to βhCG ratio was equimolar until 10 weeks of gestation when it increased almost fourfold until term (P<0·0001). Finally, the free fraction of the total circulating αhCG subunit represented 5–7% in early pregnancy but reached 60–70% in the last trimester (P<0·0001). In contrast, the free fraction of the total βhCG subunit decreased slightly from 4–5% of total β subunit in early pregnancy to 2–3% at term (P<0·0001).

The present study suggests that thermal dissociation of hCG is a useful method with which to calibrate immunoassays on a molar basis in order to assess circulating levels of the heterodimer and its subunits.

Journal of Endocrinology (1994) 140, 513–520