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Omer Turker Thyroidology Unit, Department of Nuclear Medicine, GATA Haydarpasa, Istanbul, Turkey
Department of Nuclear Medicine, Faculty of Medicine, Ege University, Izmir, Turkey
Department of Nuclear Medicine, Sifa Hospital, Izmir, Turkey

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Kamil Kumanlioglu Thyroidology Unit, Department of Nuclear Medicine, GATA Haydarpasa, Istanbul, Turkey
Department of Nuclear Medicine, Faculty of Medicine, Ege University, Izmir, Turkey
Department of Nuclear Medicine, Sifa Hospital, Izmir, Turkey

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Inanc Karapolat Thyroidology Unit, Department of Nuclear Medicine, GATA Haydarpasa, Istanbul, Turkey
Department of Nuclear Medicine, Faculty of Medicine, Ege University, Izmir, Turkey
Department of Nuclear Medicine, Sifa Hospital, Izmir, Turkey

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Ismail Dogan Thyroidology Unit, Department of Nuclear Medicine, GATA Haydarpasa, Istanbul, Turkey
Department of Nuclear Medicine, Faculty of Medicine, Ege University, Izmir, Turkey
Department of Nuclear Medicine, Sifa Hospital, Izmir, Turkey

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peroxidase antibody (TPOAb) and in thyroid-stimulating hormone (TSH)-receptor antibody concentrations in patients with AIT ( Schmidt et al. 1998 ), a significant decrease in the mean serum TPOAb levels was also noted with a daily intake of 200 μg (2.53 μmol

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G. MILHAUD
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P. RIVAILLE
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M. S. MOUKHTAR
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E. BINET
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J. C. JOB
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SUMMARY

Thyrotrophin-releasing hormone (TRH) was synthesized by the solid phase technique, administered to 13 children, and the time-course changes in the serum level of thyroid-stimulating hormone (TSH) assessed. In eight normal children, peak levels of TSH occurred 20 min after the injection, and circulating TSH remained significantly raised for 60 min. In three hypothyroid children, the increase in serum TSH was much greater than in normal children, suggesting the existence of large pituitary TSH stores. In two hypopituitary children with TSH deficiency, TSH reserves seemed normal. One of these patients had a craniopharyngioma; after operation, the increase in serum TSH was reduced. These results show that assay of serum TSH after administration of synthetic TRH provides a test which distinguishes pituitary from hypothalamic defects affecting TSH secretion.

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Z Zhang Department of Endocrinology and Metabolism, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, the Netherlands

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P H Bisschop Department of Endocrinology and Metabolism, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, the Netherlands

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E Foppen Department of Endocrinology and Metabolism, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, the Netherlands

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H C van Beeren Department of Endocrinology and Metabolism, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, the Netherlands

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A Kalsbeek Department of Endocrinology and Metabolism, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, the Netherlands
Hypothalamic Integration Mechanisms, Netherlands Institute for Neuroscience (NIN), Amsterdam, Amsterdam, the Netherlands

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A Boelen Department of Endocrinology and Metabolism, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, the Netherlands

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E Fliers Department of Endocrinology and Metabolism, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, the Netherlands

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) administration of T 3 in the rat PVN or VMH region. We implanted T 3 -containing or control pellets bilaterally into either the PVN or the VMH region of rats for a period of 28 days. Plasma T 3 , T 4 , and TSH concentrations were measured at regular time

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E Oliveira Department of Physiological Sciences, Laboratory of Lipids, Department of Applied Nutrition, Roberto Alcantara Gomes Biology Institute

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E G Moura Department of Physiological Sciences, Laboratory of Lipids, Department of Applied Nutrition, Roberto Alcantara Gomes Biology Institute

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A P Santos-Silva Department of Physiological Sciences, Laboratory of Lipids, Department of Applied Nutrition, Roberto Alcantara Gomes Biology Institute

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A T S Fagundes Department of Physiological Sciences, Laboratory of Lipids, Department of Applied Nutrition, Roberto Alcantara Gomes Biology Institute

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A S Rios Department of Physiological Sciences, Laboratory of Lipids, Department of Applied Nutrition, Roberto Alcantara Gomes Biology Institute

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Y Abreu-Villaça Department of Physiological Sciences, Laboratory of Lipids, Department of Applied Nutrition, Roberto Alcantara Gomes Biology Institute

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J F Nogueira Neto Department of Physiological Sciences, Laboratory of Lipids, Department of Applied Nutrition, Roberto Alcantara Gomes Biology Institute

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M C F Passos Department of Physiological Sciences, Laboratory of Lipids, Department of Applied Nutrition, Roberto Alcantara Gomes Biology Institute
Department of Physiological Sciences, Laboratory of Lipids, Department of Applied Nutrition, Roberto Alcantara Gomes Biology Institute

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P C Lisboa Department of Physiological Sciences, Laboratory of Lipids, Department of Applied Nutrition, Roberto Alcantara Gomes Biology Institute

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was 2.8% (T 4 ) and 3.6% (T 3 ). TSH was measured by specific RIA, using a rat TSH kit supplied by the National Institute of Health (NIH, USA) and expressed in terms of the reference preparation provided (RP-3). The intra-assay variation was 2.3%, with

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J Trojan
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M Theodoropoulou
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KH Usadel
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GK Stalla
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L Schaaf
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Enhanced sialylation of thyrotropin (TSH) prolongs its metabolic clearance rate and thus increases the hormone's in vivo bioactivity. This has been shown for hypothyroid rats and for recombinant human TSH, but there are few data on the sialylation of human serum TSH. The aim of this work was to further study sialylated human serum TSH, its precursors bearing terminal galactose residues, and the role of pharmacological doses of thyrotropin-releasing hormone (TRH) on their secretion under different degrees of primary hypothyroidism. We analyzed serum TSH in patients with subclinical (n = 9) and overt primary hypothyroidism (n = 13) compared with euthyroid individuals (n = 12) and human standard pituitary TSH (IRP 80/558). Blood was drawn before and 30 min after intravenous administration of 200 micrograms TRH, and TSH was purified by immunoaffinity concentration. The content of sialylated (sialo-) TSH and isoforms bearing terminal galactose (Gal-TSH, asialo-Gal-TSH) was measured by Ricinus communis (RCA 120) affinity chromatography in combination with enzymatic cleavage of sialic acid residues. TSH immunoreactivity was measured by an automated second generation TSH immunoassay. Pituitary TSH contained 16.5 +/- 0.8% Gal-TSH. In euthyroid individuals the proportion of Gal-TSH was 14.6 +/- 1.9%, whereas TSH in patients with subclinical and overt primary hypothyroidism contained 23.9 +/- 3.5% (P < 0.05 vs euthyroid individuals) and 21.1 +/- 1.7% Gal-TSH respectively. The mean ratio of asialo-Gal TSH was 23.8 +/- 0.6% for pituitary TSH, 35.7 +/- 4.2% in euthyroid individuals, 48.0 +/- 3.3% in patients with subclinical, and 61.5 +/- 3.8% (P < 0.001 vs euthyroid individuals) in patients with overt primary hypothyroidism. For pituitary TSH the calculated proportion of sialo-TSH was 6.5 +/- 0.2%, for euthyroid individuals 20.3 +/- 2.8%, for patients with subclinical hypothyroidism 24.1 +/- 3.0%, and for patients with overt primary hypothyroidism 40.7 +/- 3.0% (P < 0.001 vs euthyroid individuals). The proportions of Gal-TSH, asialo-Gal-TSH, and sialo-TSH did not differ significantly before and after TRH administration in the individuals studied. Our data show that patients with subclinical and overt primary hypothyroidism have a markedly increased proportion of serum TSH isoforms bearing terminal galactose and sialic acid residues, which may represent a mechanism for the further stimulation of thyroid function. Pharmacological doses of TRH cause an increased quantity of TSH to be released, but do not significantly alter the proportion of sialylated or terminally galactosylated TSH isoforms.

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S. R. Page
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A. H. Taylor
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W. Driscoll
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M. Baines
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R. Thorpe
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A. P. Johnstone
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S. S. Nussey
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G. St J. Whitley
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ABSTRACT

The mechanism by which monoclonal antibodies enhance the biological activity of a number of hormones is poorly understood. One such antibody (GC73), which binds to human but not bovine TSH, enhances the bioactivity of human TSH in vivo. We have investigated whether GC73 enhancement of TSH bioactivity involves potentiation of hormone-receptor activation assessed by the cyclic AMP (cAMP) responses of both primary human thyrocyte cultures and a TSH-responsive human thyrocyte cell line (SGHTL-45). GC73 had no effect on basal cAMP production. In contrast to its enhancement of the bioactivity of human TSH in vivo, it markedly inhibited the cAMP response to 1 and 10 mU human TSH/ml in primary thyrocytes. This effect was dose-dependent with neutralization of the bioactivity of TSH occurring at 2 mg GC73/ml. GC73 had no effect on the bioactivity of bovine TSH. In contrast, a second anti-TSH monoclonal antibody (TC12), which binds to both human and bovine TSH, inhibited the bioactivity of both species of TSH. Similar results were obtained using SGHTL-45 cells, although the peak concentrations of cAMP were lower. We conclude that binding of GC73 to human TSH resulted in inhibition rather than enhancement of the in-vitro biological activity of human TSH. We suggest that GC73 enhancement of human TSH bioactivity seen in vivo does not result from a mechanism involving potentiation of receptor activation by human TSH.

Journal of Endocrinology (1990) 126, 333–340

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Alicia J Klecha Centro de Estudios Farmacológicos y Botánicos (CEFYBO), CONICET, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, piso 15, Primera Cátedra de Farmacología, 1121 Buenos Aires, Argentina
Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junin 956, 1113 Buenos Aires, Argentina
Instituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires, AV. Combatients de Malvinas 3105, 1427 Buenos Aires, Argentina

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Ana M Genaro Centro de Estudios Farmacológicos y Botánicos (CEFYBO), CONICET, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, piso 15, Primera Cátedra de Farmacología, 1121 Buenos Aires, Argentina
Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junin 956, 1113 Buenos Aires, Argentina
Instituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires, AV. Combatients de Malvinas 3105, 1427 Buenos Aires, Argentina

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Gabriela Gorelik Centro de Estudios Farmacológicos y Botánicos (CEFYBO), CONICET, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, piso 15, Primera Cátedra de Farmacología, 1121 Buenos Aires, Argentina
Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junin 956, 1113 Buenos Aires, Argentina
Instituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires, AV. Combatients de Malvinas 3105, 1427 Buenos Aires, Argentina

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María Laura Barreiro Arcos Centro de Estudios Farmacológicos y Botánicos (CEFYBO), CONICET, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, piso 15, Primera Cátedra de Farmacología, 1121 Buenos Aires, Argentina
Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junin 956, 1113 Buenos Aires, Argentina
Instituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires, AV. Combatients de Malvinas 3105, 1427 Buenos Aires, Argentina

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Dafne Magalí Silberman Centro de Estudios Farmacológicos y Botánicos (CEFYBO), CONICET, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, piso 15, Primera Cátedra de Farmacología, 1121 Buenos Aires, Argentina
Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junin 956, 1113 Buenos Aires, Argentina
Instituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires, AV. Combatients de Malvinas 3105, 1427 Buenos Aires, Argentina

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Mariano Schuman Centro de Estudios Farmacológicos y Botánicos (CEFYBO), CONICET, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, piso 15, Primera Cátedra de Farmacología, 1121 Buenos Aires, Argentina
Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junin 956, 1113 Buenos Aires, Argentina
Instituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires, AV. Combatients de Malvinas 3105, 1427 Buenos Aires, Argentina

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Silvia I Garcia Centro de Estudios Farmacológicos y Botánicos (CEFYBO), CONICET, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, piso 15, Primera Cátedra de Farmacología, 1121 Buenos Aires, Argentina
Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junin 956, 1113 Buenos Aires, Argentina
Instituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires, AV. Combatients de Malvinas 3105, 1427 Buenos Aires, Argentina

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Carlos Pirola Centro de Estudios Farmacológicos y Botánicos (CEFYBO), CONICET, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, piso 15, Primera Cátedra de Farmacología, 1121 Buenos Aires, Argentina
Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junin 956, 1113 Buenos Aires, Argentina
Instituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires, AV. Combatients de Malvinas 3105, 1427 Buenos Aires, Argentina

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Graciela A Cremaschi Centro de Estudios Farmacológicos y Botánicos (CEFYBO), CONICET, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, piso 15, Primera Cátedra de Farmacología, 1121 Buenos Aires, Argentina
Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junin 956, 1113 Buenos Aires, Argentina
Instituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires, AV. Combatients de Malvinas 3105, 1427 Buenos Aires, Argentina

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:10 with PBS, pH 7.2, and Millipore filtered) every day for 30 days. In this way almost undetectable values of thyroid-stimulating hormone (TSH) were obtained. Mice injected with the vehicle alone were used as controls. The anti-thyroid drug PTU

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Yusuke Taguchi Division of Life Science, Graduate School of Science and Engineering, Saitama University, National Institute of Occupational Safety and Health, 255 Shimo-okubo, Sakura-ku, Saitama 338-8570, Japan

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Yoshie Tasaki Division of Life Science, Graduate School of Science and Engineering, Saitama University, National Institute of Occupational Safety and Health, 255 Shimo-okubo, Sakura-ku, Saitama 338-8570, Japan

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Kiyoshi Terakado Division of Life Science, Graduate School of Science and Engineering, Saitama University, National Institute of Occupational Safety and Health, 255 Shimo-okubo, Sakura-ku, Saitama 338-8570, Japan

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Kenichi Kobayashi Division of Life Science, Graduate School of Science and Engineering, Saitama University, National Institute of Occupational Safety and Health, 255 Shimo-okubo, Sakura-ku, Saitama 338-8570, Japan
Division of Life Science, Graduate School of Science and Engineering, Saitama University, National Institute of Occupational Safety and Health, 255 Shimo-okubo, Sakura-ku, Saitama 338-8570, Japan

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Takeo Machida Division of Life Science, Graduate School of Science and Engineering, Saitama University, National Institute of Occupational Safety and Health, 255 Shimo-okubo, Sakura-ku, Saitama 338-8570, Japan

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Tetsuya Kobayashi Division of Life Science, Graduate School of Science and Engineering, Saitama University, National Institute of Occupational Safety and Health, 255 Shimo-okubo, Sakura-ku, Saitama 338-8570, Japan

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growth in contrast to dw mice ( Yoshida et al . 1994 ). In grt mice, plasma concentrations of thyroxine (T 4 ) are significantly lower, whereas levels of thyroid-stimulating hormone (TSH) are greatly elevated ( Yoshida et al . 1994 , Tomita et al

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Shuhang Xu
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Guofang Chen
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Wen Peng
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Kostja Renko Division of Endocrinology, Institute for Experimental Endocrinology, Department of Medicine, St Hedwig Hospital and

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Michael Derwahl
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symporter peroxidase ( TPO ) and sodium iodide ( NIS ( SLC5A5 )) were markedly decreased with a maximal inhibition of TSH-induced NIS expression. In conclusion, oestrogen stimulated the growth and simultaneously inhibited the differentiation of thyroid

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Raúl M Luque Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain
Department of Cell Biology, Physiology and Immunology, University of Córdoba, Cordoba, Spain
Hospital Universitario Reina Sofia (HURS), Cordoba, Spain
CIBER de la Fisiopatología de la Obesidad y Nutrición (CIBERobn), Madrid, Spain

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Rhonda D Kineman Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago and Research and Development Division, Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois, USA

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), follicle-stimulating hormone (FSH), luteinizing hormone (LH), adrenocorticotropic hormone (ACTH) and thyroid-stimulating hormone (TSH)) release and expression. In addition, to better understand the mechanisms behind these actions, we used pharmacological

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