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A McMaster Medicine, Faculty of Life Sciences, Centre for Molecular
Medicine, Faculty of Life Sciences, Centre for Molecular

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T Chambers Medicine, Faculty of Life Sciences, Centre for Molecular

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Q-J Meng Medicine, Faculty of Life Sciences, Centre for Molecular

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S Grundy Medicine, Faculty of Life Sciences, Centre for Molecular

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A S I Loudon Medicine, Faculty of Life Sciences, Centre for Molecular

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R Donn Medicine, Faculty of Life Sciences, Centre for Molecular
Medicine, Faculty of Life Sciences, Centre for Molecular

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D W Ray Medicine, Faculty of Life Sciences, Centre for Molecular

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There is increasing evidence that temporal factors are important in allowing cells to gain additional information from external factors, such as hormones and cytokines. We sought to discover how cell responses to glucocorticoids develop over time, and how the response kinetics vary according to ligand structure and concentration, and hence have developed a continuous gene transcription measurement system, based on an interleukin-6 (IL-6) luciferase reporter gene. We measured the time to maximal response, maximal response and integrated response, and have compared these results with a conventional, end point glucocorticoid bioassay. We studied natural glucocorticoids (corticosterone and cortisol), synthetic glucocorticoids (dexamethasone) and glucocorticoid precursors with weak, or absent bioactivity. We found a close correlation between half maximal effective concentration (EC50) for maximal response, and for integrated response, but with consistently higher EC50 for the latter. There was no relation between the concentration of ligand and the time to maximal response. A comparison between conventional end point assays and real-time measurement showed similar effects for dexamethasone and hydrocortisone, with a less effective inhibition of IL-6 seen with corticosterone. We profiled the activity of precursor steroids, and found pregnenolone, progesterone, 21-hydroxyprogesterone and 17-hydroxyprogesterone all to be ineffective in the real-time assay, but in contrast, progesterone and 21-hydroxyprogesterone showed an IL-6 inhibitory activity in the end point assay. Taken together, our data show how ligand concentration can alter the amplitude of glucocorticoid response, and also that a comparison between real-time and end point assays reveals an unexpected diversity of the function of glucocorticoid precursor steroids, with implications for human disorders associated with their overproduction.

Article Type:
Research Article
DOI:
https://doi.org/10.1677/JOE-07-0639
Volume/Issue:
Volume 197: Issue 2
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Joachim M Weitzel Institute of Reproductive Biology, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany

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Torsten Viergutz Institute of Reproductive Biology, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany

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Dirk Albrecht Institute of Microbiology, Ernst-Moritz-Arndt-University, Greifswald, Germany

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Rupert Bruckmaier Veterinary Physiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland

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Marion Schmicke Clinic for Cattle, Endocrinology Laboratory, University of Veterinary Medicine Hannover, Hannover, Germany

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Armin Tuchscherer Institute of Genetics and Biometry, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany

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Franziska Koch Institute of Nutritional Physiology ‘Oskar Kellner’, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany

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Björn Kuhla Institute of Nutritional Physiology ‘Oskar Kellner’, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany

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, Weitzel & Iwen 2011 ). The THRs belong to a group of transcription factors whose gene regulation function is depending on the presence or absence of their particular ligand (i.e. TH). Liganded and un-liganded THRs recruit cofactors which convert chromatin

Article Type:
Research Article
DOI:
https://doi.org/10.1530/JOE-17-0066
Volume/Issue:
Volume 234: Issue 2
Open access
Nan Yang Manchester Centre for Nuclear Hormone Research in Disease and Institute of Human Development, Institute of Cardiovascular Sciences, Faculty of Medical and Human Sciences, University of Manchester, AV Hill Building, Oxford Road, Manchester, M13 9PT, UK

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Giorgio Caratti Manchester Centre for Nuclear Hormone Research in Disease and Institute of Human Development, Institute of Cardiovascular Sciences, Faculty of Medical and Human Sciences, University of Manchester, AV Hill Building, Oxford Road, Manchester, M13 9PT, UK

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Louise M Ince Manchester Centre for Nuclear Hormone Research in Disease and Institute of Human Development, Institute of Cardiovascular Sciences, Faculty of Medical and Human Sciences, University of Manchester, AV Hill Building, Oxford Road, Manchester, M13 9PT, UK

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Toryn M Poolman Manchester Centre for Nuclear Hormone Research in Disease and Institute of Human Development, Institute of Cardiovascular Sciences, Faculty of Medical and Human Sciences, University of Manchester, AV Hill Building, Oxford Road, Manchester, M13 9PT, UK

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Peter J Trebble Manchester Centre for Nuclear Hormone Research in Disease and Institute of Human Development, Institute of Cardiovascular Sciences, Faculty of Medical and Human Sciences, University of Manchester, AV Hill Building, Oxford Road, Manchester, M13 9PT, UK

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Cathy M Holt Manchester Centre for Nuclear Hormone Research in Disease and Institute of Human Development, Institute of Cardiovascular Sciences, Faculty of Medical and Human Sciences, University of Manchester, AV Hill Building, Oxford Road, Manchester, M13 9PT, UK

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David W Ray Manchester Centre for Nuclear Hormone Research in Disease and Institute of Human Development, Institute of Cardiovascular Sciences, Faculty of Medical and Human Sciences, University of Manchester, AV Hill Building, Oxford Road, Manchester, M13 9PT, UK

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Laura C Matthews Manchester Centre for Nuclear Hormone Research in Disease and Institute of Human Development, Institute of Cardiovascular Sciences, Faculty of Medical and Human Sciences, University of Manchester, AV Hill Building, Oxford Road, Manchester, M13 9PT, UK

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repeated three times. Graphs show mean± s.e.m . * P <0.05. NS, not significant. To define the role of JNK on endogenous gene regulation, again cells were transfected with activated JNK and then analysed by qRT-PCR. As expected both MT1X and FKBP5 were

Article Type:
Research Article
DOI:
https://doi.org/10.1530/JOE-14-0456
Volume/Issue:
Volume 223: Issue 2
Open access
Georgina G J Hazell
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Song T Yao
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James A Roper
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Eric R Prossnitz LINE, University of New Mexico, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, UK

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Anne-Marie O'Carroll
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Stephen J Lolait
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614 – 623 . Burbach JPH Luckman SM Murphy D Gainer H 2001 Gene regulation in the magnocellular hypothalamo-neurohypophysial system . Physiological Reviews 81 1198 – 1266 . Carmeci C Thompson DA Ring HZ Francke U Weigel RJ

Article Type:
Research Article
DOI:
https://doi.org/10.1677/JOE-09-0066
Volume/Issue:
Volume 202: Issue 2
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Craig L Doig School of Clinical and Experimental Medicine, Centre for Endocrinology, Diabetes and Metabolism, University of Birmingham, Birmingham B15 2TT, UK

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Jamila Bashir School of Clinical and Experimental Medicine, Centre for Endocrinology, Diabetes and Metabolism, University of Birmingham, Birmingham B15 2TT, UK

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Agnieszka E Zielinska School of Clinical and Experimental Medicine, Centre for Endocrinology, Diabetes and Metabolism, University of Birmingham, Birmingham B15 2TT, UK

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Mark S Cooper School of Clinical and Experimental Medicine, Centre for Endocrinology, Diabetes and Metabolism, University of Birmingham, Birmingham B15 2TT, UK

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Paul M Stewart School of Clinical and Experimental Medicine, Centre for Endocrinology, Diabetes and Metabolism, University of Birmingham, Birmingham B15 2TT, UK

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Gareth G Lavery School of Clinical and Experimental Medicine, Centre for Endocrinology, Diabetes and Metabolism, University of Birmingham, Birmingham B15 2TT, UK

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muscle, adipocytes from p65 overexpression transgenic mice had elevated 11β-HSD1 at the mRNA and protein level, but show no evidence for direct gene regulation ( Lee et al . 2013 ). In this context, NF-κB was acting as a positive regulator in a model of

Article Type:
Research Article
DOI:
https://doi.org/10.1530/JOE-13-0494
Volume/Issue:
Volume 220: Issue 3
Open access
Young Hoon Son Department of Biochemistry and Molecular Biology, Institute of Human–Environment Interface Biology, Department of Rehabilitation Medicine, Seoul National University College of Medicine, 103 Daehak‐ro, Jongno‐Gu, Seoul 110‐799, Korea

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Seok-Jin Lee Department of Biochemistry and Molecular Biology, Institute of Human–Environment Interface Biology, Department of Rehabilitation Medicine, Seoul National University College of Medicine, 103 Daehak‐ro, Jongno‐Gu, Seoul 110‐799, Korea

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Ki-Baek Lee Department of Biochemistry and Molecular Biology, Institute of Human–Environment Interface Biology, Department of Rehabilitation Medicine, Seoul National University College of Medicine, 103 Daehak‐ro, Jongno‐Gu, Seoul 110‐799, Korea

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Jin-Haeng Lee Department of Biochemistry and Molecular Biology, Institute of Human–Environment Interface Biology, Department of Rehabilitation Medicine, Seoul National University College of Medicine, 103 Daehak‐ro, Jongno‐Gu, Seoul 110‐799, Korea

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Eui Man Jeong Department of Biochemistry and Molecular Biology, Institute of Human–Environment Interface Biology, Department of Rehabilitation Medicine, Seoul National University College of Medicine, 103 Daehak‐ro, Jongno‐Gu, Seoul 110‐799, Korea
Department of Biochemistry and Molecular Biology, Institute of Human–Environment Interface Biology, Department of Rehabilitation Medicine, Seoul National University College of Medicine, 103 Daehak‐ro, Jongno‐Gu, Seoul 110‐799, Korea

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Sun Gun Chung Department of Biochemistry and Molecular Biology, Institute of Human–Environment Interface Biology, Department of Rehabilitation Medicine, Seoul National University College of Medicine, 103 Daehak‐ro, Jongno‐Gu, Seoul 110‐799, Korea

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Sang-Chul Park Department of Biochemistry and Molecular Biology, Institute of Human–Environment Interface Biology, Department of Rehabilitation Medicine, Seoul National University College of Medicine, 103 Daehak‐ro, Jongno‐Gu, Seoul 110‐799, Korea

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In-Gyu Kim Department of Biochemistry and Molecular Biology, Institute of Human–Environment Interface Biology, Department of Rehabilitation Medicine, Seoul National University College of Medicine, 103 Daehak‐ro, Jongno‐Gu, Seoul 110‐799, Korea
Department of Biochemistry and Molecular Biology, Institute of Human–Environment Interface Biology, Department of Rehabilitation Medicine, Seoul National University College of Medicine, 103 Daehak‐ro, Jongno‐Gu, Seoul 110‐799, Korea

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://www.cbil.upenn.edu/cgibin , http://alggen.lsi.upc.es/cgibin/promo_v3 , and http://www.gene-regulation.com/cgi-bin . Transfection and luciferase assays C2C12 cells (2×10 4 ) were seeded into a 12-well plate and cultured for 24 h. The cells were then transfected with reporter

Article Type:
Research Article
DOI:
https://doi.org/10.1530/JOE-14-0490
Volume/Issue:
Volume 225: Issue 1
Open access
Jin Yu Department of Gynecology of Traditional Chinese Medicine, Changhai Hospital, Naval Medical University, Shanghai, China

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Yuhuan Liu Department of Gynecology and Obstetrics, Changhai Hospital, Naval Medical University, Shanghai, China

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Danying Zhang Department of Gynecology of Traditional Chinese Medicine, Changhai Hospital, Naval Medical University, Shanghai, China

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Dongxia Zhai Department of Gynecology of Traditional Chinese Medicine, Changhai Hospital, Naval Medical University, Shanghai, China

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Linyi Song Department of Gynecology of Traditional Chinese Medicine, Changhai Hospital, Naval Medical University, Shanghai, China

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Zailong Cai Department of Biochemistry and Molecular Biology, Naval Medical University, Shanghai, China

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Chaoqin Yu Department of Gynecology of Traditional Chinese Medicine, Changhai Hospital, Naval Medical University, Shanghai, China

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sequence from −507 to −325 bp was analyzed using the AliBaba2.1 software ( http://www.gene-regulation.com/pub/programs/alibaba2/index.html ), and the potential transcriptional regulatory elements, including C/EBPalp, Oct1, HNF1, NF1, GATA1, NF-EM5 and GCN4

Article Type:
Research Article
DOI:
https://doi.org/10.1530/JOE-18-0678
Volume/Issue:
Volume 240: Issue 3
Open access
L A Nolan Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, UK

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A Levy Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, UK

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Cellular distribution and gene regulation of estrogen receptors alpha and beta in the rat pituitary gland . Endocrinology 139 3976 – 3983 . Nishihara E Nagayama Y Inoue S Hiroi H Muramatsu M Yamashita S Koji T 2000 Ontogenetic changes

Article Type:
Research Article
DOI:
https://doi.org/10.1677/JOE-08-0474
Volume/Issue:
Volume 200: Issue 3
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Yu Wang Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing, China
The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
National Clinical Research Center for Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China

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Fan Li Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing, China
The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
National Clinical Research Center for Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China

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Xiaoqian Gao Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing, China
The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
National Clinical Research Center for Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China

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Huahui Yu Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing, China
The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
National Clinical Research Center for Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China

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Zhiyong Du Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing, China
The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
National Clinical Research Center for Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China

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Linyi Li Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing, China
The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
National Clinical Research Center for Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China

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Yunhui Du Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing, China
The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
National Clinical Research Center for Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China

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Chaowei Hu Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing, China
The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
National Clinical Research Center for Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China

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Yanwen Qin Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing, China
The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
National Clinical Research Center for Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China

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-5p reduces cholesterol levels, we used TargetScan8.0 and miRWALK to predict possible target genes regulated by miR-181d-5p. This analysis identified PCSK9 , which is associated with the LDL-C clearance pathway. The mechanism of miRNA-mediated gene

Article Type:
Research Article
DOI:
https://doi.org/10.1530/JOE-23-0402
Volume/Issue:
Volume 262: Issue 3
Open access
Shona Wood Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK

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Andrew Loudon Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK

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.1242/jcs.088500 ) Featherstone K White MRH Davis JRE 2012 The prolactin gene: a paradigm of tissue-specific gene regulation with complex temporal transcription dynamics . Journal of Neuroendocrinology 24 977 – 990 . ( doi:10.1111/j.1365

Article Type:
Review Article
DOI:
https://doi.org/10.1530/JOE-14-0141
Volume/Issue:
Volume 222: Issue 2
Open access