bluuebunny/crossref_metadata_2025_split huggingface dataset:
No changes of peripheral insulin resistance in polycystic ovary syndrome after long-term reduction of endogenous androgens with leuprolide
Authors: Lasco Antonino , Cucinotta Domenico , Gigante Alfonso , Denuzzo Giulia , Pedulla Marilena , Trifiletti Aldo , Frisina Nicola 
Published: December 2008

Lasco A, Cucinotta D, Gigante A, Denuzzo G, Pedulla M, Trifiletti A, Frisina N. No changes of peripheral insulin resistance in polycystic ovary syndrome after long-term reduction of endogenous androgens with leuprolide. Eur J Endocrinol 1995;133:718–22. ISSN 0804–4643
The aim of this study was to investigate the relationship between plasma insulin levels, peripheral insulin sensitivity and androgen secretion in ten patients with polycystic ovary syndrome and in six obese women as compared with six normal-weight control subjects. During a euglycemic–hyperinsulinemic clamp no significant change of testosterone, androstenedione or dehydroepiandrosterone sulfate plasma levels was observed in the two groups of patients or in the control subjects; insulin sensitivity was clearly reduced and was similar in polycystic ovary patients and in obese women, in spite of the different plasma androgen levels. A long-term (5 months) androgen suppression with the gonadotropin-releasing hormone agonist leuprolide was not able to improve significantly the insulin sensitivity. These results demonstrate that the short-term hyperinsulinemia achieved with the clamp technique does not affect androgen secretion and that insulin resistance, measured with the same technique, is not influenced by long-term suppression of plasma androgen levels in polycystic ovary syndrome.
A Lasco, Via Faustina e Tertullo 19, 98100 Messina, Italy
Effects of epidermal growth factor and transforming growth factor alpha on the mouse trophoblast outgrowth in vitro
Authors: Machida Toshifumi , Taga Michiyoshi , Minaguchi Hiroshi 
Published: December 2008

Machida T, Taga M, Minaguchi H. Effects of epidermal growth factor and transforming growth factor alpha on the mouse trophoblast outgrowth in vitro. Eur J Endocrinol 1995;133:741–6. ISSN 0804–4643
In order to analyze the involvement of growth factors in the implantation mechanism, we examined the direct effects of epidermal growth factor (EGF) and transforming growth factor alpha (TGF-α) on trophoblast outgrowth of the mouse blastocyst in vitro. ICR mouse blastocysts were cultured for 4 days on a culture plate in medium containing EGF or TGF-α or conditioned medium obtained from cultured endometrial epithelial cells. Blastocysts were also co-cultured with endometrial epithelial cells. The trophoblast outgrowth of these cultured blastocysts was observed daily and the percentage of outgrowing embryos was calculated and analyzed statistically by the chi-squared test. Analysis for the specific binding of 125I-EGF in outgrown trophoblasts was carried out by autoradiography. The coculture (days 3 and 4) and the presence of EGF (10 ng/ml, day 4), TGF-α (1 ng/ml, day 3; 10 ng/ml, days 2 and 3; 50 ng/ml, days 2–4) or conditioned medium (days 3 and 4) significantly stimulated the rate of trophoblast outgrowth. Preincubation of the conditioned medium with monoclonal anti-EGF or anti-TGF-α antibody suppressed the stimulatory effect of the conditioned medium on trophoblast outgrowth. The specific 125I-EGF binding in outgrown trophoblasts was demonstrated by autoradiography. These results suggest that EGF and TGF-α play an important role in the implantation process by directly stimulating trophoblast development.
Michiyoshi Taga, Department of Obstetrics and Gynecology, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236, Japan
Angiotensin II modulates steroidogenesis in granulosa and theca in the rabbit ovary: its possible involvement in atresia
Authors: Féral C , Le Gall S , Leymarie P 
Published: December 2008

Féral C, Le Gall S, Leymarie P. Angiotensin II modulates steroidogenesis in granulosa and theca in the rabbit ovary: its possible involvement in atresia. Eur J Endocrinol 1995;133:747–53. ISSN 0804–4643
Accumulating evidence has shown the ovary of mammals to contain an intrinsic renin–angiotensin system that has been ascribed an autocrine-paracrine role. The present study in the female rabbit ovary investigated the putative in vitro action of angiotensin II (A II) on basal and gonadotropin-induced steroidogenesis. Ovarian follicles from immature female rabbits treated with pregnant mare's serum gonadotropin (PMSG) were dissected out and a complete separation of the theca interna from the granulosa layer was performed, to demonstrate that A II affects separately the two individual cellular components of the follicular wall. We could show that theca is a source of estradiol whose production under human chorionic gonadotropin (hCG) stimulation was reduced by A II. At the same time, A II increased the in vitro hCG-stimulated secretion of testosterone by theca. In granulosa, A II decreased hCG-stimulated aromatization of androstenedione to estradiol but did not alter the release of hCG-stimulated progesterone production. These results suggest that A II could induce locally an increase in follicular fluid androgen/estrogen ratio and possibly participate in causing atresia.
C. Féral, EP CNRS 009, Laboratoire de Biochimie, CHU Caen, F-14032 Caen Cedex, France
An open 36-month study of lipid changes with growth hormone in adults: lipid changes following replacement of growth hormone in adult acquired growth hormone deficiency
Authors: Garry P , Collins P , Devlin JG 
Published: December 2008

Garry P. Collins P. Devlin JG. An open 36 month study of lipid changes with growth hormone in adults: lipid changes following replacement of growth hormone in adult acquired growth hormone deficiency. Eur J Endocrinol 1996:134:61–6. ISSN 0804–4643
Interest in adult growth hormone replacement has increased since identification of the associated vascular morbidity and mortality. Although total cholesterol and low density lipoprotein reduction and high density lipoprotein increases are anticipated, reports are conflicting and there is no uniformity in lipoprotein(a) changes. In 1990 we commenced an open trial of therapy with human recombinant GH and now have results to 36 months for 21 patients. Deficiency status was confirmed by insulin stress test with flat GH response <2.0 ng/ml, mean insulin-like growth factor-I value 122 ng/ml (±69 SD). Lipoprotein(a) was measured by monoclonal assay. Lipid analysis yields two subgroups: baseline cholesterol levels of greater or less than 6.22 mmol/l, with hypercholesterolaemic patients showing an enhanced hypolipaemic response. ANOVA was utilized, with 95% confidence limits. The most significant changes are of reductions in cholesterol and low density lipoprotein: the rate of change is greatest at 6 and 12 months but not sustained to 36 months. High density lipoprotein rises as expected, not to full significance. Lipoprotein(a) levels rose significantly in six patients of the cohort, and the increase was sustained over 36 months.
JG Devlin, Department of Endocrinology, Beaumont Hospital. Dublin 9. Ireland
Patient with monoclonal gammopathy, thyrotoxicosis, pretibial myxedema and thyroid-associated ophthalmopathy; demonstration of direct binding of autoantibodies to the thyrotropin receptor
Authors: Tonacchera Massimo , Costagliola Sabine , Cetani Filomena , Ducobu Jean , Stordeur Patrick , Vassart Gilbert , Ludgate Marian 
Published: December 2008

Tonacchera M. Costagliola S, Cetani F, Ducobu J. Stordeur P. Vassart G. Ludgate M. Patient with monoclonal gammopathy, thyrotoxicosis, pretibial myxedema and thyroid-associated ophthalmopathy: demonstration of direct binding of autoantibodies to the thyrotropin receptor. Eur J Endocrinol 1996:134:97–103. ISSN 0804–4643
We describe a patient with monoclonal gammopathy who subsequently developed thyrotoxicosis, pretibial myxedema and thyroid-associated ophthalmopathy. The pathogenesis of thyrotoxicosis in Graves' disease is due to the presence of autoantibodies that mimic the action of thyrotropin (TSH). called thyroid-stimulating antibodies (TS-ab): these antibodies may or may not inhibit the binding of TSH to the receptor (thyroid-binding inhibiting immunoglobulin, TBII). The patient's immunoglobulins were TS-ab positive and TBII negative when measured on CHO cells expressing the human TSH receptor. The pathogenetic link between the thyroid, orbit and skin is yet to be established but several candidate shared antigens have been proposed, including the TSH receptor itself. The monoclonal immunoglobulins were in evidence before the symptoms of pretibial myxedema, thyrotoxicosis and ophthalmopathy, In addition, the patient had no autoantibodies to thyroglobulin or thyroperoxidase, which are classic markers of thyroid autoimmunity. This combination led us to postulate that the monoclonal gammopathy could be the cause of all the observed pathology. One method to test this hypothesis would be to show that the monoclonal immunoglobulin is a TS-ab. Various methods were used to separate the monoclonal from the polyclonal components of the patient's serum. Preparative isoelectric focusing enabled us to obtain fractions containing only the monoclonal (as revealed by polyacrylamide gel electrophoresis), which were devoid of TS-ab activity (measured as cAMP accumulation in CHO cells expressing the human TSH receptor in a hypotonic bioassay). Subsequently, different oligoclonal fractions were shown to have varying degrees of TS-ab activity, with one fraction having faint biological activity and able to recognize a recombinant TSH receptor preparation in a Western blot. In conclusion, the monoclonal antibody does not seem to be responsible for the thyrotoxicosis, pretibial myxedema and ophthalmopathy. We confirm previous data showing that TSH receptor antibodies in patients with Graves' disease are heterogeneous in nature and we present the first demonstration of autoantibodies capable of binding the TSH receptor but devoid of TBII activity.
Massimo Tonacchera, Institut de Recherche Interdisciplinaire, Université Libre de Bruxelles, Campus Erasme, 808 Route de Lennik, 1070 Bruxelles
Thyroid hormone induces the generation of a novel putative protein in piscine ovarian follicle that stimulates the conversion of pregnenolone to progesterone
Authors: Bhattacharya S , Guin S , Bandyopadhyay A , Jana NR , Halder S 
Published: December 2008

Bhattacharya S, Guin S, Bandyopadhyay A, Jana NR, Halder S. Thyroid hormone induces the generation of a novel putative protein in piscine ovarian follicle that stimulates the conversion of pregnenolone to progesterone. Eur J Endocrinol 1996:134:128–35. ISSN 0840–4643.
Ovarian follicles were collected from the perch belonging to the vitellogenic stage and incubated in vitro for 4 h in the absence (control) or presence of triiodothyronine (T3). Addition of T3 (40 ng/ml) to the follicle incubation caused a two-fold increase of [3H] pregnenolone conversion to radiolabelled progesterone (P4) as compared to the control. The increase in P4 formation in the ovarian follicle could be blocked completely by the inhibitors of protein synthesis, actinomycin D and cycloheximide (50 μg/ ml), suggesting a protein or peptide mediator of the T3 stimulatory effect. To search for this mediator, ovarian follicles from the control or T3 incubate were homogenized and ultracentrifuged and different fractions were added separately to fresh follicle incubations. Only the 100 000g supernatant from T3 incubate showed a significant (p < 0.01) increase in P4 formation, while the corresponding supernatant from control follicle incubations had no such stimulatory effect. Trypsin or heat destroyed this augmentory effect. Based on its ability to stimulate the conversion of radiolabelled pregnenolone to P4 in the ovarian follicle, the T3-induced protein (TIP) was purified to homogeneity by employing Sephadex G-75 gel filtration, FPLC Mono-Q and FPLC Superose-6 chromatography. Sodium dodecyl sulphate polyacrylamide gel electrophoresis of purified TIP showed it to be a 52 K monomer protein. Addition of TIP in increasing concentrations to follicle incubations caused a linear increase in P4 formation. Experiments with radiolabelled TIP ([125 I] TIP) indicate its entry through the follicular cell membrane within the limited period of incubation. Results suggest that TIP activates ovarian 3β-hydroxysteroid dehydrogenase enzyme, thus effecting a greater conversion of pregnenolone to P4.
S. Bhattacharya, Department of Zoology, Visva-Bharati University. Santiniketan 731 235, West Bengal, India
Bone mineral density in immigrants from southern China to Denmark. A cross-sectional study
Authors: Wang Q , Ravn P , Wang S , Overgaard K , Hassager C , Christiansen C 
Published: December 2008

Wang Q, Ravn P, Wang S, Overgaard K, Hassager C, Christiansen C. Bone mineral density in immigrants from southern China to Denmark: a cross-sectional study. Eur J Endocrinol 1996;134:163–7. ISSN 0804–4643
Immigration from Japan to USA has been shown to increase bone mineral density (BMD) and body fat in women. The effects of immigration between other geographical areas on bone mass and body composition are largely unknown, especially in men. In the present study, we measured bone mass and body composition by dual energy X-ray absorptiometry (Hologic QDR-2000) in 73 healthy premenopausal women (age 35 ± 8 years) and 69 men (age 40 ± 12 years) who had immigrated from southern China to Denmark 2 months to 36 years ago. The BMD measurements (Total BMD, trunk BMD and leg BMD) were related positively to years since immigration (YSI) (R2 = 0.10–0.16, p < 0.05) in premenopausal women, but not in men. Fat distribution was related mainly to age in both premenopausal women and men (R2 = 0.16–0.26, p < 0.05). For comparison, we included 51 white, Danish premenopausal women (age 36 ± 6 years). Chinese premenopausal women with a YSI below or equal to 12 years (N = 38) had significantly lower total and regional BMD (trunk, legs, arms) (p < 0.05), while women with a YSI above 12 years (N = 35) had significantly lower BMD in the legs only (p < 0.05) when compared to the Danish premenopausal women. After correction for age, weight and height, Chinese premenopausal women with a YSI below or equal to 12 years still had significantly lower BMD in all regions (4–7%, p < 0.05), whereas no differences in BMD were found between Chinese premenopausal women with a YSI above 12 years compared with Danish premenopausal women. In conclusion, Chinese premenopausal women who immigrated to Denmark more than 12 years ago have a similar BMD to that of Danish premenopausal women. In the group who immigrated less than 12 years ago, a significantly lower BMD was found.
P Ravn, Center for Clinical and Basic Research, Ballerup Byvej 222, DK-2750 Ballerup, Denmark
Body composition and energy expenditure in thyroidectomized patients during short-term hypothyroidism and thyrotropin-suppressive thyroxine therapy
Authors: Wolf Matthias , Weigert Andrea , Kreymann Georg 
Published: December 2008

Wolf M, Weigert A, Kreymann G. Body composition and energy expenditure in thyroidectomized patients during short-term hypothyroidism and thyrotropin-suppressive thyroxine therapy. Eur J Endocrinol 1996;134:168–73. ISSN 0804–4643
Thyroid hormone levels are a major determinant of energy balance and are thought to modify body composition by their effects on metabolism of lipids, carbohydrate and protein. The present study evaluates changes of body composition and basal energy expenditure (BEE) in thyroidectomized patients studied during short-term profound hypothyroidism while off all thyroid hormone before diagnostic whole-body I-imaging and while on thyrotrophin-suppressive thyroxine therapy. Basal energy expenditure was assessed by indirect calorimetry, and four-point body impedance analysis was used to estimate body composition. Patients were compared with healthy controls matched with respect to sex, age, height and weight. Compared to healthy controls the percentages of body water and body cell mass were significantly lower while the percentage of fat was significantly higher in patients during short-term hypothyroidism. Weight did not change significantly when patients were put on thyroxine treatment, but body fat (–0.95 ± 2.25 kg, p < 0.01) decreased while body water (+0.94 ± 1.31 kg, p < 0.01) and body cell mass (+0.9 ± 2.5 kg, p < 0.05) increased. With thyroxine replacement, body composition was not significantly different between patients and controls. Compared to healthy controls, BEE was significantly lower in patients without thyroxine replacement (5265 ± 766 kJ/24 h vs 6362 ± 992 kJ/24 h; p < 0.001). With thyroxine treatment, BEE increased (6492 ± 967 kJ/24 h) but was not significantly different from the controls (p 0.05). Neither body composition nor BEE was significantly different in a subgroup of thyroxine-treated patients with free triiodothyronine or thyroxine values above the normal range. In conclusion, both body composition and energy expenditure showed significant changes when patients were deprived of thyroid hormone. However, no evidence of excess metabolic effects of thyroid hormone during thyrotrophin-suppressive thyroxine therapy was found.
Matthias Wolf, Medizinische Kern- und Poliklinik, Universitäts-Krankenhaus Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany
Secretory rhythm of vasopressin in healthy subjects with inversed sleep–wake cycle: evidence for the existence of an intrinsic regulation
Authors: Nadal Miguel 
Published: December 2008

Nadal M. Secretory rhythm of vasopressin in healthy subjects with inversed sleep–wake cycle: evidence for the existence of an intrinsic regulation. Eur J Endocrinol 1996;134:174–6. ISSN 0804–4643
The objective of this paper was to find out if the higher night levels of vasopressin described in previous studies are a manifestation of a permanent and stable rhythm bound to the different periods of the day or if they are independent of them and due to other causes. Vasopressin secretion was studied in a group of seven healthy subjects with an inverted sleep–wake cycle (night workers who sleep and rest during the day). The study was performed during the last week of their working period after at least 3 weeks of continuous night shift. Plasma samples for vasopressin determination were taken every 4 h during a 24-h period while the subjects were performing their normal night work and with their usual sleeping habits during the day. Plasma osmolality, electrolytes and blood pressure were also assessed during the test. In contrast to previous studies where higher nocturnal values have been reported, we found significantly higher vasopressin levels during the day, giving as a whole a characteristic pattern with the highest vasopressin levels measured at 16.00 h followed by a progressive decrement that reached its nadir at 04.00 h. The total measured secretion of vasopressin was significantly higher during the day than during the night (p = 0.0313). No significant difference was found, on the other hand, between day samples, with the exception of samples taken at 16.00 h and at 12.00 h (p = 0.031). Plasma osmolality and electrolytes were within the normal range during the test and no statistical difference was observed at the various points. It was concluded that the secretion of vasopressin is higher during sleep and rest time and lower during the active part of the 24 h. The secretory pattern of vasopressin is not bound to the different periods of the day as such, nor to variations in plasma osmolality or electrolytes. It seems therefore reasonable to assume that the secretion of vasopressin has an intrinsic daily rhythm that is not related to known regulatory agents but is modulated by other unidentified factors. Several hypotheses are discussed.
Miguel Nadal, Department of Internal Medicine (Endocrinology), Skellefteå Hospital, S-931 86 Skellefteå, Sweden
Low frequency of p53 mutations in human thyroid tumors; p53 and Ras mutation in two out of fifty-six thyroid tumours
Authors: Salvatore Domenico , Celetti Angela , Fabien Nicole , Paulin Christian , Martelli Maria Luisa , Battaglia Caterina , Califano Daniela , Monaco Carmen , Viglietto Giuseppe , Santoro Massimo , Fusco Alfredo 
Published: December 2008

Salvatore D, Celetti A, Fabien N, Paulin C, Martelli ML, Battaglia C, Califano D, Monaco C, Viglietto G, Santoro M, Fusco A. Low frequency of p53 mutations in human thyroid tumors; p53 and Ras mutation in two out of fifty-six thyroid tumours. Eur J Endocrinol 1996;134:177–83. ISSN 0804–4643
Objective: p53 is a well-known nuclear phosphoprotein encoded by a suppressor gene known to be mutated in various kinds of human tumours. A relationship between p53 gene mutation and tumour progression seems to be a common feature of several neoplasias. Desing: In order to investigate the role of p53 mutations in human thyroid tumours, DNA samples derived from fifty-six neoplastic tissues, ranging from benign adenomas to undifferentiated carcinomas, were examined for the presence of p53 gene mutations. Methods: The analysis has been conducted using polymerase chain reaction (PCR) amplification of the exons 5–9 of the p53 gene followed by single strand conformation polymorphism (SSCP) and sequence analyses. Results: One anaplastic carcinoma and one papillary carcinoma showed p53 gene mutations in exons 5 and 8, respectively. A cell line established from the papillary carcinoma showed the same mutation present in the original tumour. Both p53 mutations were heterozygous. The p53 positive samples were analysed for other genetic alterations frequently detected in human thyroid carcinomas (mutations of the RET, TRK, and ras oncogenes): both p53-mutated samples proved to be mutated at level of codon 13 of the c-Ki-ras gene. Conclusions: Our data confirm that p53 gene alterations are rare in well-differentiated thyroid tumours, that they are an important requirement for the establishment in culture of human thyroid carcinoma cell lines, and that they can be associated with other genetic alterations, namely ras mutations, in the malignant progression of thyroid tumours.
Alfredo Fusco, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Facoltà di Medicina e Chirurgia, via S. Pansini 5, 80131, Napoli, Italy