bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnosis and management of pheochromocytomas in patients with multiple endocrine neoplasia type 2—relevance of specific mutations in the RET proto-oncogene
Authors: Frank-Raue Karin , Kratt Thomas , Höppner Wolfgang , Buhr Heinz , Ziegler Reinhard , Raue Friedhelm 
Published: December 2008

Frank-Raue K, Kratt T, Höppner W, Buhr H, Ziegler R, Raue F. Diagnosis and management of pheochromocytomas in patients with multiple endocrine neoplasia type 2—relevance of specific mutations in the RET proto-oncogene. Eur J Endocrinol 1996;135:222–5. ISSN 0804–4643
It has been suggested that specific mutations in the RET proto-oncogene correlate with clinical manifestation of the multiple endocrine neoplasia type 2 (MEN 2) syndrome. We retrospectively analyzed 61 patients with MEN 2, 28 with associated pheochromocytoma, regarding the relevance of specific mutations in the RET proto-oncogene and the diagnostic sensitivity of catecholamine screening and localization procedures. The present study shows that the position of the RET mutation is related to disease phenotype; codon 634 mutations are predictive of families predisposed to pheochromocytoma. In 18% of our patients, the diagnosis of pheochromocytoma preceded detection of medullary thyroid carcinoma. Therefore, mutation analysis of the RET gene should be performed in apparently "sporadic" cases of pheochromocytoma to confirm or exclude MEN 2. The most sensitive biochemical marker for pheochromocytoma in MEN 2 is 24-h urinary epinephrine excretion. Computed tomography, magnetic resonance imaging and MIBG scintigraphy are all highly sensitive methods to localize pheochromocytoma. We conclude that, in all families with MEN 2, mutational analysis of the RET proto-oncogene should be performed, both to identify gene carriers for MEN 2 and to identify specific mutations that are more strongly associated with pheochromocytoma.
Karin Frank-Raue, Department of Internal Medicine, Endocrinology & Metabolism, Bergheimer Straße 58, 69115 Heidelberg, Germany
Quantification of the negative feedback mechanism between pituitary and thyroid in subjects with normal thyroid function
Authors: Sydow Karin , Emrich Dieter , Gefeller Olaf , Schreivogel Inge 
Published: December 2008

Sydow K, Emrich D, Gefeller O, Schreivogel I. Quantification of the negative feedback mechanism between pituitary and thyroid in subjects with normal thyroid function. Eur J Endocrinol 1996;135:316–21. ISSN 0804–4643
Using sufficiently sensitive and precise assays, we systematically investigated the correlation between thyrotropin, thyroglobulin, index of free thyroxine and index of free triiodothyronine after different doses of thyroxine (25, 50, 100, 150 μg), which were administered daily for 10 days to individuals with normal thyroid function and in a control group. Analysis of the data using relative median values expressing changes to basal values before administration of thyroxine yielded the following results: (i) thyrotropin and thyroglobulin decreased monoexponentially, depending on the doses of thyroxine administered; (ii) the extent of their decrease showed a linear correlation with the dose of thyroxine administered and was greater for thyrotropin than for thyroglobulin; (iii) the relative velocity of their decrease increased monoexponentially with the dose of thyroxine and did not differ between thyrotropin and thyroglobulin. These results provide strong evidence for a clear quantitative reaction of the feedback mechanism and confirm that the secretion of thyroglobulin is a physiological process dependent on thyrotropin. The high intra-individual variations obtained for thyrotropin were probably due to its pulsatile secretion.
D. Emrich, Department of Nuclear Medicine, University of Göttingen, Robert-Koch-Str. 40, D-37075 Göttingen, Germany
Determination of free follistatin levels in sera of normal subjects and patients with various diseases
Authors: Sakamoto Yukihiro , Shintani Yasumi , Harada Kazuyo , Abe Masahiro , Shitsukawa Keiji , Saito Shiro 
Published: December 2008

Sakamoto Y. Shintani Y, Harada K, Abe M, Shitsukawa K, Saito S. Determination of free follistatin levels in sera of normal subjects and patients with various diseases. Eur J Endocrinol 1996:135:345–51. ISSN 0804–4643
We developed an assay system for measuring free follistatin by using an anti-follistatin mouse monoclonal antibody and [125I]activin A. The sensitivity of this assay was 0.5 μg/l and crossreactivities with inhibin. luteinizing hormone, follicle-stimulating hormone and growth hormone were all less than 0.5%. The dose-response curves of human sera and follicular fluid were parallel to the standard curve, and the follicular fluid contained a large amount of follistatin (6.4 ± 0.5 mg/l, mean ± SEM; N = 13). The within- and between-assay coefficients of variation calculated from the analysis of serum samples of four different concentrations were 3.3–7.8% and 3.9–11.0%, respectively. The recovery rates of free follistatin at five different doses were 86.4–102.4%. When activin A was added to the same sample, free follistatin recovery rate declined dose-dependently. Gel filtration analyses of human serum and follicular fluid resulted in a single peak corresponding to authentic follistatin. Using this assay, free follistatin concentrations in sera were measured in normal, pregnant and diseased subjects. The free follistatin level in serum of normal adults was 3.5 ± 0.2 μg/l (N = 60), which was significantly elevated in pregnant women (16.7 ± 1.3 μg/l, N = 56), and in patients with chronic liver disease (8.1 ± 1.1 μg/l, N = 20), chronic renal failure (6.7 ± 0.9 μg/l, N = 42), advanced solid cancer (8.5 ± 1.0 μg/l, N = 39) and hematological malignancies (6.8 ± 1.0 μg/l, N = 18). These data indicated that the free follistatin concentration in serum is detectable and varies during pregnancy and in various diseased states.
Yukihiro Sakamoto, First Department of Internal Medicine, School of Medicine, The University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima 770, Japan
Interleukin 10 inhibits insulin release from and nitric oxide production in rat pancreatic islets
Authors: Laffranchi Renato , Spinas Giatgen A 
Published: December 2008

Laffranchi R, Spinas GA. Interleukin 10 inhibits insulin release from and nitric oxide production in rat pancreatic islets. Eur J Endocrinol 1996;135:374–8. ISSN 0804–4643
Interleukin 10 was found to prevent cytokine-induced nitric oxide production in murine macrophages. Because, in rat islets, interleukin 1β induces β-cell dysfunction, mainly due to overproduction of nitric oxide, we studied if this effect could be counteracted by interleukin 10. Rat pancreatic islets were cultured for 24 h in the presence or absence of 0.02–20 ng/ml recombinant human interleukin 10. Interleukin 10 dose-dependently inhibited insulin secretion with maximal inhibition (27 ±4%, p < 0.05) at 2 ng/ml without impairment of islet cell viability. However, incubation of pancreatic islets with interleukin 10 resulted in a 61.5% decrease of nitric oxide production. Co-incubation of islets with interleukin 10 (2 ng/ml) and recombinant human interleukin 1β (0.15 ng/ml) resulted in a more pronounced suppression of basal insulin release than with interleukin 1β alone (55 ± 3.6% vs 44 ± 3.6% with interleukin 1β alone, p < 0.05) but did not reduce interleukin 1β-stimulated NO production or reverse the effect of interleukin 1β on cell viability. Thus, in pancreatic islets interleukin 10 is not capable of counteracting the interleukin 1β-induced β-cell dysfunction, but rather enhances the inhibitory effect of interleukin 1β by a different mechanism.
Renato Laffranchi, Division of Endocrinology and Metabolism, Department of Internal Medicine, University Hospital, Rämistrasse 100, CH-8091 Zürich, Switzerland
Effects of gonadotropin-releasing hormone on bioactivity of follicle-stimulating hormone (FSH) and microstructure of FSH, luteinizing hormone and sex hormone-binding globulin in a testosterone-based contraceptive trial: evaluation of responders and non-responders
Authors: Simoni Manuela , Peters Jörg , Behre Hermann M , Kliesch Sabine , Leifke Eckhard , Nieschlag Eberhard 
Published: December 2008

Simoni M, Peters J, Behre HM, Kliesch S, Leifke E, Nieschlag E. Effects of gonadotropin-releasing hormone on bioactivity of follicle-stimulating hormone (FSH) and microstructure of FSH. luteinizing hormone and sex hormone-binding globulin in a testosterone-based contraceptive trial: evaluation of responders and non-responders. Eur J Endocrinol 1996;135:433–9. ISSN 0804–4643
Only a proportion of normal men participating in testosterone-based contraceptive trials develop azoospermia (responders). This study analyzed whether serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and sex hormone-binding globulin (SHBG) are qualitatively different between responders and non-responders. Determination of in vitro bioactive FSH after stimulation with gonadotropin-releasing hormone (GnRH) and analysis of molecular heterogeneity of serum FSH. LH and SHBG was carried out by chromatofocusing and concanavalin-A affinity chromatography in eight men who had participated in a previous contraceptive study with testosterone buciclate. Blood was withdrawn at 15-min intervals on two basal occasions and 30, 45 and 60 min after iv administration of GnRH (100 μg). Pools of sera were separated by chromatofocusing in the pH range 3–6 and by lectin chromatography on concanavalin A. Immunoreactive FSH, LH and SHBG were assayed in the eluates. Bioactive FSH was analyzed by the rat Sertoli cell bioassay. Serum bioactive FSH increased after GnRH stimulation, without significant differences between responders and non-responders. The chromatofocusing profiles of serum FSH showed a significant shift towards the less acidic region after GnRH. The isoform distribution was similar in responders and non-responders. No significant differences were found in the relative proportion of FSH, LH and SHBG retained by concanavalin A. It is concluded that the extent of suppression of sperm production by androgen administration cannot be foreseen either on the basis of the response of bioactive FSH to GnRH administration or from the glycosylation pattern of serum FSH, LH and SHBG.
E Nieschlag, Institute of Reproductive Medicine of the University, Domagkstr. 11, D-48129 Münster, Germany
Presence and localization of endothelin receptor in the rat ovary and its regulation by pituitary gonadotropins
Authors: Otani Hisako , Yamoto Mareo , Fujinaga Hiroyuki , Nakano Ryosuke 
Published: December 2008

Otani H, Yamoto M. Fujinaga H, Nakano R. Presence and localization of endothelin receptor in the rat ovary and its regulation by pituitary gonadotropins. Eur J Endocrinol 1996:135:449–54. ISSN 0804–4643
In the present study we examined the regulation of receptors for endothelin 1 (ET-1) in rat granulosa cells. We examined the localization and regulation of ET receptors in immature rat ovary and the effects of ET-1 on steroidogenesis in cultured rat granulosa cells. The ovaries used in autoradiography were derived from pregnant mare serum gonadotropin and human chorionic gonadotropin-treated immature rats. Granulosa cells were obtained from diethylstilbestrol-treated immature rats and incubated with 125I-ET-1. Granulosa cells were cultured with ET-1 in the presence or absence of ovine follicle-stimulating hormone. The concentrations of sex steroid hormones in conditioned media were measured by radioimmunoassay. The binding site for ET-1 was localized in the granulosa cells, but not in thecal and luteal cells. Follicle-stimulating hormone (FSH) induced a dose-dependent increase in specific binding for ET-1 to cultured rat granulosa cells. In contrast. luteinizing hormone (LH) induced a dose-dependent decrease in specific binding for ET-1 to cultured rat granulosa cells. Conversely, treatment with prolactin and several sex steroid hormones had no effects on the specific binding of ET-1. Treatment with ET-1 inhibited FSH-stimulated accumulation of progesterone and estradiol in cultured rat granulosa cells. The results indicate that both FSH and LH influence the expression of ET-1 receptor, and that ET-1 may play a regulatory role in the ontogeny of the granulosa cell.
Ryosuke Nakano, Department of Obstetrics and Gynecology. Wakayama Medical College, 27 Shichibancho, Wakayama, 640, Japan
Rhythmicity of luteinizing hormone secretion expressed in vitro
Authors: Lewy Hadas , Naor Zvi , Ashkenazi Israel E 
Published: December 2008

Lewy H, Naor Z, Ashkenazi IE. Rhythmicity of luteinizing hormone secretion expressed in vitro. Eur J Endocrinol 1996;135:455–63. ISSN 0804–4643
In the present study we explored the possibility that the pituitary functions as an autonomous clock and is capable of generating rhythms of luteinizing hormone (LH) release independently of hypothalamic control. Pituitaries from estrous or diestrous day 1 female mice were perifused separately with Medium-199. Effluent samples were collected at 10-min intervals and assayed for LH levels. Fourier analysis and curve-fit analysis served to elucidate the presence of prominent periods whose significance was then determined by best-fit cosinor. The latter method was used to determine additional parameters for the significant rhythm. All perifused pituitaries exhibited LH release patterns that were composed of significantly long ultradian rhythms (approximately 16 and 8 h, p < 0.001). Continuous stimulation with gonadotropin-releasing hormone (GnRH) or estradiol did not alter the periods of the observed rhythms but affected other rhythm parameters. Gonadotropin-releasing hormone increased the mesor of the rhythm and estradiol increased the amplitude. The results indicate that pituitary gonadotropes are capable of producing rhythms of LH release for a long duration in vitro, in the absence of hypothalamic control. Both GnRH and estradiol affect different rhythm parameters but do not change the periods of these rhythms.
Israel E Ashkenazi, Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
Primary culture of human thyrocytes in Transwell bicameral chamber: thyrotropin promotes polarization and epithelial barrier function
Authors: Nilsson Mikael , Husmark Johanna , Nilsson Bengt , Tisell Lars-Erik , Ericson Lars E 
Published: December 2008

Nilsson M, Husmark J, Nilsson B, Tisell L-E, Ericson LE. Primary culture of human thyrocytes in Transwell bicameral chamber: thyrotropin promotes polarization and epithelial barrier function. Eur J Endocrinol 1996;135:469–80. ISSN 0804–4643
Epithelial properties of thyrocytes are difficult to maintain in conventional cell culture systems. We used bicameral chambers (Transwell™) in attempts to establish a functional epithelium of thyrocytes of human origin. Thyroid follicle segments were isolated by collagenase digestion of paradenomatous tissue obtained at surgery for follicular adenoma and of tissue from glands with Graves' disease. After careful separation from connective tissue and single cells by centrifugation, the follicles were plated at high density on the collagen-coated filter of the chambers and cultured in Eagle's essential medium (EMEM) containing 10% fetal calf serum (FCS) or Coon's modified Hams medium enriched with five or six factors (5H, 6H); the latter media contained 5% FCS without (5H) or with (6H) thyrotropin (TSH). The follicles were converted into a confluent cell layer, which had similar DNA content irrespective of type of medium, after 4–6 days. Cells grown in EMEM or 5H established a transepithelial electrical resistance (R) of 200–500Ω·cm2 and was impermeable to [3H]inulin, indicating the formation of epithelial junctions. Addition of 6H to confluent cells initially cultured in EMEM or 5H caused a further increase of R, maximally to 1500 Ω·cm2, along with a rise of the transepithelial potential difference; 6H promoted the monolayer formation of cells, increased the number of apical microvilli and reinforced the junctional distribution of actin, cadherin and ZO-1; 6H also enhanced the polarized secretion of [3H]leucine-labeled thyroglobulin into the apical medium. Cells from Graves' thyroid tissue established an epithelium on the filter with similar characteristics to that of normal thyrocytes; some platings contained in addition large numbers of HLA-DR positive cells with a dendritic shape. HLA-DR expression was generally absent in EMEM- or 5H-grown thyrocytes, but appeared in limited areas of the cell layer after 6H and was expressed by all epithelial cells after interferon-gamma stimulation for 48 h. We conclude that human thyrocytes form a tight and polarized epithelium when cultured on permeable filters. The polarized structure and function of the cells are positively regulated by TSH. The culture system may be useful in studies addressing the role of the epithelial phenotype (cell polarity and tight barrier) in normal thyroid function as well as in pathological processes in the thyroid, such as autoimmunity, cell transformation and tumor progression.
Mikael Nilsson, Institute of Anatomy and Cell Biology, Göteborg University, Medicinaregatan 3, S-413 90 Göteborg, Sweden
l-Arginine is unlikely to exert neuroendocrine effects in humans via the generation of nitric oxide
Authors: Korbonits Márta , Trainer Peter J , Fanciulli Giuseppe , Oliva Osvaldo , Pala Alessandra , Dettori Alessandra , Besser Michael , Delitala Giuseppe , Grossman Ashley B 
Published: December 2008

Korbonits M, Trainer PJ, Fanciulli G, Oliva O, Pala A, Dettori A, Besser GM, Delitala G, Grossman AB. l-Arginine is unlikely to exert neuroendocrine effects in humans via the generation of nitric oxide. Eur J Endocrinol 1996;135:543–7. ISSN 0804–4643
There is now considerable evidence that nitric oxide is an important neuroregulatory agent, but there has been very little investigation of its possible role in neuroendocrine mechanisms in humans. We have investigated the effects of two nitric oxide precursors, l-arginine and molsidomine, under basal conditions on the pituitary hormones growth hormone (GH), prolactin, luteinizing hormone, folliclestimulating hormone, thyrotrophin, adrenocorticotrophin (ACTH) and vasopressin, and also on serum cortisol; we have also studied the effect of l-arginine on circulating prolactin, ACTH and cortisol in normal human subjects under hypoglycaemic stress. l-Arginine stimulated both GH and prolactin release under basal conditions but had no effect on the other hormones studied, while the nitric oxide donor molsidomine showed no effect on any hormone studied. l-Arginine potentiated the hypoglycaemia-stimulated release of ACTH but did not influence the rise in GH. The current studies suggest that the effects of l-arginine on the stimulation of GH and prolactin release are unlikely to be mediated via the generation of nitric oxide.
A Grossman, Department of Endocrinology, St Bartholomew's Hospital, West Smithfield, London EC1A 7BE, UK
Follow-up of bone mineral density in 27 cases of anorexia nervosa
Authors: Maugars Yves M , Berthelot Jean-Marie M , Forestier Romain , Mammar Nadia , Lalande Sylvia , Venisse Jean-Luc , Prost Alain M 
Published: December 2008

Maugars YM, Berthelot J-MM, Forestier R, Mammar N, Lalande S, Venisse J-L, Prost AM. Follow-up of bone mineral density in 27 cases of anorexia nervosa. Eur J Endocrinol 1996;135:591–7. ISSN 0804–4643
Cortical and trabecular bone loss can lead to osteoporosis in chronic forms of anorexia nervosa (AN). As there is some debate about the reversibility of this condition, we performed a longitudinal follow-up study of 27 cases in which clinical, biological, X-ray and lumbar and femoral neck dual photon absorptiometry examinations were conducted every 6 months for up to 30 months. Three groups were distinguished: G1, untreated amenorrheic AN (N = 14, total follow-up 126 months); G2, effectively treated AN (N = 11, total follow-up 192 months), with two subgroups: fluoride (N = 5) and estrogen (N = 6); and G3, remitting AN with normalization of the gonadic function (N = 2, total follow-up 36 months). Results were adjusted for each patient to a 6-month variation. Semestrial variations in lumbar bone mineral density (BMD) were −2.1 ± 1.3%, +2.8 ± 1.5% and −0.3 ± 1.3% (mean ± sem), respectively for G1, G2 and G3; those for femoral neck BMD semestrial variations were −5.9 ± 2.1%, −3.8 ± 1.2% and −1.0 ± 0.6%. Femoral neck and lumbar BMD variations for G1 were mainly correlated positively with bone-forming markers (serum osteocalcin, alkaline phosphatase) and negatively with initial lumbar BMD. Estrogen alone increased lumbar BMD by +1.4 ± 2.3% every 6 months but did not stabilize femoral neck BMD (−3.5 ± 1.4%). Fluoride increased lumbar BMD by 4.8 ± 1.8%. Both lumbar and femoral neck BMD were stabilized in the remission group (−0.3 ± 1.3% and −1.0 ± 0.6%), despite half of the follow-up time with amenorrhea. In conclusion, untreated AN is associated with a marked trabecular and cortical bone loss (4–10% per year), which can lead to osteoporotic fractures. In prevention of bone loss, the efficacy of estrogen is difficult to investigate in AN, even with a well-controlled trial. Our study could provide argument that, when the observance of this preventive treatment is assessed, lumbar BMD can be stabilized in chronic forms of AN.
Yves Maugars, CHU de Nantes, Service de Rhumatologie, 44035 Nantes, Cédex 01, France
Spironolactone therapy in hypertrichosis
Authors: Darendeliler F , Baş F , Balaban S , Bundak R , Demirkol D , Saka N , Günöz H 
Published: December 2008

Darendeliler F, Baş F, Balaban S, Bundak R, Demirkol D, Saka N, Günöz H. Spironolactone therapy in hypertrichosis. Eur J Endocrinol 1996;135:604–8. ISSN 0804–4643
Although regarded as a benign condition, simple hypertrichosis may be very disturbing to a child cosmetically. An abnormality in androgen metabolism has been implied in the etiology of simple hypertrichosis recently. This study was undertaken to investigate the effect of spironolactone therapy for its antiandrogenic property in 12 prepubertal girls with hypertrichosis with no underlying etiology. The girls, with a mean age of 6.9 (1.2) years, had normal height and bone age. Basal hormone levels and adrenocorticotropin stimulation test results were in the normal ranges. Pelvic and adrenal ultrasound did not reveal pathology. Total and medullary hair width were measured from hair taken from preauricular, anterior midthigh, distal and proximal forearm areas. Spironolactone was started at an oral dose of 25 and increased to 100 mg·m−2·day−1 twice daily for 1 year. Total hair width decreased significantly in the preauricular and anterior midthigh regions up to 6–9 months of treatment. Medullary hair width, which was affected by therapy to a greater extent, decreased significantly in all regions up to 6 months. Both total and medullary hair width showed a tendency to increase afterwards. No side effects were encountered. Spironolactone may be used in the treatment of simple hypertrichosis; however, more data are needed to clarify the efficacy and safety of anti-androgen therapy in hypertrichosis.
Feyza Darendeliler, Istanbul Tip Fakültesi, Çocuk Kliniǧi, Çapa 34390, Istanbul, Turkey