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Alvaro Souto Padron Laboratório de Fisiologia Endócrina Doris Rosenthal, Laboratório de Biologia do Exercício, Instituto de Biofísica Carlos Chagas Filho and Instituto de Pesquisa Translacional em Saúde e Ambiente na Região Amazônica (INPeTAM), CCS-Bloco G- Cidade Universitria, Ilha do Fundo, Rio de Janeiro 21949-900, Brazil

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Ruy Andrade Louzada Neto Laboratório de Fisiologia Endócrina Doris Rosenthal, Laboratório de Biologia do Exercício, Instituto de Biofísica Carlos Chagas Filho and Instituto de Pesquisa Translacional em Saúde e Ambiente na Região Amazônica (INPeTAM), CCS-Bloco G- Cidade Universitria, Ilha do Fundo, Rio de Janeiro 21949-900, Brazil
Laboratório de Fisiologia Endócrina Doris Rosenthal, Laboratório de Biologia do Exercício, Instituto de Biofísica Carlos Chagas Filho and Instituto de Pesquisa Translacional em Saúde e Ambiente na Região Amazônica (INPeTAM), CCS-Bloco G- Cidade Universitria, Ilha do Fundo, Rio de Janeiro 21949-900, Brazil

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Thiago Urgal Pantaleão Laboratório de Fisiologia Endócrina Doris Rosenthal, Laboratório de Biologia do Exercício, Instituto de Biofísica Carlos Chagas Filho and Instituto de Pesquisa Translacional em Saúde e Ambiente na Região Amazônica (INPeTAM), CCS-Bloco G- Cidade Universitria, Ilha do Fundo, Rio de Janeiro 21949-900, Brazil

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Maria Carolina de Souza dos Santos Laboratório de Fisiologia Endócrina Doris Rosenthal, Laboratório de Biologia do Exercício, Instituto de Biofísica Carlos Chagas Filho and Instituto de Pesquisa Translacional em Saúde e Ambiente na Região Amazônica (INPeTAM), CCS-Bloco G- Cidade Universitria, Ilha do Fundo, Rio de Janeiro 21949-900, Brazil

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Renata Lopes Araujo Laboratório de Fisiologia Endócrina Doris Rosenthal, Laboratório de Biologia do Exercício, Instituto de Biofísica Carlos Chagas Filho and Instituto de Pesquisa Translacional em Saúde e Ambiente na Região Amazônica (INPeTAM), CCS-Bloco G- Cidade Universitria, Ilha do Fundo, Rio de Janeiro 21949-900, Brazil

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Bruno Moulin de Andrade Laboratório de Fisiologia Endócrina Doris Rosenthal, Laboratório de Biologia do Exercício, Instituto de Biofísica Carlos Chagas Filho and Instituto de Pesquisa Translacional em Saúde e Ambiente na Região Amazônica (INPeTAM), CCS-Bloco G- Cidade Universitria, Ilha do Fundo, Rio de Janeiro 21949-900, Brazil

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Monique da Silva Leandro Laboratório de Fisiologia Endócrina Doris Rosenthal, Laboratório de Biologia do Exercício, Instituto de Biofísica Carlos Chagas Filho and Instituto de Pesquisa Translacional em Saúde e Ambiente na Região Amazônica (INPeTAM), CCS-Bloco G- Cidade Universitria, Ilha do Fundo, Rio de Janeiro 21949-900, Brazil

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João Pedro Saar Werneck de Castro Laboratório de Fisiologia Endócrina Doris Rosenthal, Laboratório de Biologia do Exercício, Instituto de Biofísica Carlos Chagas Filho and Instituto de Pesquisa Translacional em Saúde e Ambiente na Região Amazônica (INPeTAM), CCS-Bloco G- Cidade Universitria, Ilha do Fundo, Rio de Janeiro 21949-900, Brazil

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Andrea Claudia Freitas Ferreira Laboratório de Fisiologia Endócrina Doris Rosenthal, Laboratório de Biologia do Exercício, Instituto de Biofísica Carlos Chagas Filho and Instituto de Pesquisa Translacional em Saúde e Ambiente na Região Amazônica (INPeTAM), CCS-Bloco G- Cidade Universitria, Ilha do Fundo, Rio de Janeiro 21949-900, Brazil

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Denise Pires de Carvalho Laboratório de Fisiologia Endócrina Doris Rosenthal, Laboratório de Biologia do Exercício, Instituto de Biofísica Carlos Chagas Filho and Instituto de Pesquisa Translacional em Saúde e Ambiente na Região Amazônica (INPeTAM), CCS-Bloco G- Cidade Universitria, Ilha do Fundo, Rio de Janeiro 21949-900, Brazil

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these unequivocal effects on energy metabolism, 3,5-T2 might also affect the hypothalamus–pituitary–thyroid axis. Horst et al . (1995) have shown that 3,5-T2 treatment reduced serum thyroid-stimulating hormone (TSH) and thyroxine (T 4 ) levels as well

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Anna de Lloyd Department of Child Health, Centre for Endocrine and Diabetes Sciences

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James Bursell Department of Child Health, Centre for Endocrine and Diabetes Sciences

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John W Gregory Department of Child Health, Centre for Endocrine and Diabetes Sciences

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D Aled Rees Department of Child Health, Centre for Endocrine and Diabetes Sciences

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Marian Ludgate Department of Child Health, Centre for Endocrine and Diabetes Sciences

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The TSH receptor and its role in the thyroid The established biological function of the TSH receptor (TSHR) in the thyroid gland is to regulate synthesis and secretion of thyroid hormones from follicular thyroid cells; it also plays an important

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Min Lu Department of Medicine, Molecular, Gene and Cell Medicine, Mount Sinai School of Medicine, Mount Sinai School of Medicine, Box 1055, One Gustave L Levy Place, New York, New York 10029, USA Departments of

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Reigh-Yi Lin Department of Medicine, Molecular, Gene and Cell Medicine, Mount Sinai School of Medicine, Mount Sinai School of Medicine, Box 1055, One Gustave L Levy Place, New York, New York 10029, USA Departments of
Department of Medicine, Molecular, Gene and Cell Medicine, Mount Sinai School of Medicine, Mount Sinai School of Medicine, Box 1055, One Gustave L Levy Place, New York, New York 10029, USA Departments of
Department of Medicine, Molecular, Gene and Cell Medicine, Mount Sinai School of Medicine, Mount Sinai School of Medicine, Box 1055, One Gustave L Levy Place, New York, New York 10029, USA Departments of
Department of Medicine, Molecular, Gene and Cell Medicine, Mount Sinai School of Medicine, Mount Sinai School of Medicine, Box 1055, One Gustave L Levy Place, New York, New York 10029, USA Departments of

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primarily from physical inactivity and a reduced resting metabolic rate by virtue of the accompanying dramatic elevations of thyroid-stimulating hormone (TSH) levels. Sub-clinical hypothyroidism, characterized by elevated TSH levels but normal thyroid

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P C Lisboa Laboratory of Endocrine Physiology, Laboratory of Neurophysiology, Carlos Chagas Filho Biophysic Institute, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro 20551‐030, Brazil

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E de Oliveira Laboratory of Endocrine Physiology, Laboratory of Neurophysiology, Carlos Chagas Filho Biophysic Institute, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro 20551‐030, Brazil

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A C Manhães Laboratory of Endocrine Physiology, Laboratory of Neurophysiology, Carlos Chagas Filho Biophysic Institute, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro 20551‐030, Brazil

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A P Santos-Silva Laboratory of Endocrine Physiology, Laboratory of Neurophysiology, Carlos Chagas Filho Biophysic Institute, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro 20551‐030, Brazil

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C R Pinheiro Laboratory of Endocrine Physiology, Laboratory of Neurophysiology, Carlos Chagas Filho Biophysic Institute, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro 20551‐030, Brazil

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V Younes-Rapozo Laboratory of Endocrine Physiology, Laboratory of Neurophysiology, Carlos Chagas Filho Biophysic Institute, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro 20551‐030, Brazil
Laboratory of Endocrine Physiology, Laboratory of Neurophysiology, Carlos Chagas Filho Biophysic Institute, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro 20551‐030, Brazil

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L C Faustino Laboratory of Endocrine Physiology, Laboratory of Neurophysiology, Carlos Chagas Filho Biophysic Institute, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro 20551‐030, Brazil

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T M Ortiga-Carvalho Laboratory of Endocrine Physiology, Laboratory of Neurophysiology, Carlos Chagas Filho Biophysic Institute, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro 20551‐030, Brazil

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E G Moura Laboratory of Endocrine Physiology, Laboratory of Neurophysiology, Carlos Chagas Filho Biophysic Institute, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro 20551‐030, Brazil

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thyrotropin (TSH), featuring a primary thyroid hypofunction, as well as higher serum leptin in the suckling pups, at the end of nicotine exposure. Interestingly, these animals show a very quick recovery at weaning, because these parameters were normal. In

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Takao Ando Thyroid Research Unit, Mount Sinai School of Medicine, The James J Peters VA Medical Center, Box 1055, 1 Gustave L Levy Place, New York, New York 10029, USA

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Rauf Latif Thyroid Research Unit, Mount Sinai School of Medicine, The James J Peters VA Medical Center, Box 1055, 1 Gustave L Levy Place, New York, New York 10029, USA

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Terry F Davies Thyroid Research Unit, Mount Sinai School of Medicine, The James J Peters VA Medical Center, Box 1055, 1 Gustave L Levy Place, New York, New York 10029, USA

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uncleaved holoreceptors on the cell surface than seen in thyroid cells ( Misrahi et al. 1994 , Rapoport et al. 1998 ). Deletion of the cleaved region in the TSHR ectodomain does not affect TSH binding to, nor activation of, the TSHR ( Chazenbalk et al

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Beate Karges Pediatric Endocrinology, University Children’s Hospital, University of Ulm, Prittwitzstrasse 43, D-89075 Ulm, Germany
Institute of Molecular Pharmacology, 13125 Berlin, Germany
INSERM U584, Hôpital Necker, 75006 Paris, France
Division of Endocrinology, Department of Internal Medicine, University of Ulm, 89081 Ulm, Germany

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Gerd Krause Pediatric Endocrinology, University Children’s Hospital, University of Ulm, Prittwitzstrasse 43, D-89075 Ulm, Germany
Institute of Molecular Pharmacology, 13125 Berlin, Germany
INSERM U584, Hôpital Necker, 75006 Paris, France
Division of Endocrinology, Department of Internal Medicine, University of Ulm, 89081 Ulm, Germany

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Janos Homoki Pediatric Endocrinology, University Children’s Hospital, University of Ulm, Prittwitzstrasse 43, D-89075 Ulm, Germany
Institute of Molecular Pharmacology, 13125 Berlin, Germany
INSERM U584, Hôpital Necker, 75006 Paris, France
Division of Endocrinology, Department of Internal Medicine, University of Ulm, 89081 Ulm, Germany

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Klaus-Michael Debatin Pediatric Endocrinology, University Children’s Hospital, University of Ulm, Prittwitzstrasse 43, D-89075 Ulm, Germany
Institute of Molecular Pharmacology, 13125 Berlin, Germany
INSERM U584, Hôpital Necker, 75006 Paris, France
Division of Endocrinology, Department of Internal Medicine, University of Ulm, 89081 Ulm, Germany

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Nicolas de Roux Pediatric Endocrinology, University Children’s Hospital, University of Ulm, Prittwitzstrasse 43, D-89075 Ulm, Germany
Institute of Molecular Pharmacology, 13125 Berlin, Germany
INSERM U584, Hôpital Necker, 75006 Paris, France
Division of Endocrinology, Department of Internal Medicine, University of Ulm, 89081 Ulm, Germany

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Wolfram Karges Pediatric Endocrinology, University Children’s Hospital, University of Ulm, Prittwitzstrasse 43, D-89075 Ulm, Germany
Institute of Molecular Pharmacology, 13125 Berlin, Germany
INSERM U584, Hôpital Necker, 75006 Paris, France
Division of Endocrinology, Department of Internal Medicine, University of Ulm, 89081 Ulm, Germany

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Introduction The thyrotrophin receptor (TSH-R) belongs to the family of G protein-coupled receptors (GPCRs) containing seven transmembrane helices (TMH). Since 1994, activating germline mutations of the TSH-R have been identified as

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Patricia Joseph-Bravo Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), A.P. 510-3, Cuernavaca, Morelos 62250, Mexico

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Lorraine Jaimes-Hoy Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), A.P. 510-3, Cuernavaca, Morelos 62250, Mexico

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Rosa-María Uribe Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), A.P. 510-3, Cuernavaca, Morelos 62250, Mexico

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Jean-Louis Charli Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), A.P. 510-3, Cuernavaca, Morelos 62250, Mexico

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, although the purification and identification of thyroid-stimulating hormone (TSH) spanned several decades ( Magner 2014 ). Semi-purified TSH preparations from bovine pituitaries demonstrated a similar structure to other pituitary hormones. It is composed of

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Alessandro Marsili
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Edith Sanchez Thyroid Section, Division of Endocrinology, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Harvard Institutes of Medicine, Room 644, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA

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Praful Singru Thyroid Section, Division of Endocrinology, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Harvard Institutes of Medicine, Room 644, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA

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John W Harney
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Ann Marie Zavacki
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Ronald M Lechan Thyroid Section, Division of Endocrinology, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Harvard Institutes of Medicine, Room 644, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA

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P R Larsen
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Introduction The feedback regulation of TSH secretion by thyroid hormones is mediated by the binding of 3,3′,5′-triiodothyronine (T 3 ) to the TRβ2 receptor in the pituitary and hypothalamus ( Chiamolera & Wondisford 2009 ). The acute suppression of

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Emin Umit Bagriacik Immunology Research Center, Department of Immunology, Department of Hematology, Endocrinology Department, Gazi University, 06500 Ankara, Turkey
Immunology Research Center, Department of Immunology, Department of Hematology, Endocrinology Department, Gazi University, 06500 Ankara, Turkey

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Melek Yaman Immunology Research Center, Department of Immunology, Department of Hematology, Endocrinology Department, Gazi University, 06500 Ankara, Turkey

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Rauf Haznedar Immunology Research Center, Department of Immunology, Department of Hematology, Endocrinology Department, Gazi University, 06500 Ankara, Turkey

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Gulsan Sucak Immunology Research Center, Department of Immunology, Department of Hematology, Endocrinology Department, Gazi University, 06500 Ankara, Turkey

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Tuncay Delibasi Immunology Research Center, Department of Immunology, Department of Hematology, Endocrinology Department, Gazi University, 06500 Ankara, Turkey

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Introduction The TSH receptor or the thyrotropin receptor (TSHR) is usually expressed by thyroid cells. It is a G protein-coupled receptor and signals through cAMP and inositol triphosphate (IP 3 ) pathways ( Kursawe & Paschke 2000 , Davies et al

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A. D. TOFT
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W. M. HUNTER
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W. J. IRVINE
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It has been established in animals that anterior pituitary hormones control their own secretion by regulating at a hypothalamic level the release of their hypothalamic factors (Motta, Fraschini & Martini, 1969). If a negative 'short-feedback' of thyroid-stimulating hormone (TSH) on the hypothalamus exists in man, the high plasma TSH levels of untreated primary hypothyroidism should fall markedly after the administration of bovine TSH which shares the biological, but not the immunological, properties of human TSH. This report describes the effects of bovine TSH on human plasma TSH (H-TSH) levels in patients with primary hypothyroidism.

Twenty-seven patients with untreated primary hypothyroidism were studied, of whom 20 had been treated with 131I and four by subtotal thyroidectomy for thyrotoxicosis. The remaining three patients had spontaneous primary hypothyroidism. The diagnosis of primary hypothyroidism was made on clinical grounds and on the basis of a low serum protein-bound iodine (< 3·8 μg/100 ml),

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