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Myrian Velasco Neuroscience Division, Department of Cognitive Neuroscience, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico

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Rosa Isela Ortiz-Huidobro Neuroscience Division, Department of Cognitive Neuroscience, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico

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Carlos Larqué Department of Embryology and Genetics, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico

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Yuriko Itzel Sánchez-Zamora Neuroscience Division, Department of Cognitive Neuroscience, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico

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José Romo-Yáñez Department of Gynecological and Perinatal Endocrinology, Instituto Nacional de Perinatología ‘Isidro Espinosa de los Reyes’, Mexico City, Mexico

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Marcia Hiriart Neuroscience Division, Department of Cognitive Neuroscience, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico

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, Daniel Macouzet Iturbe, and Francisco Pérez Eugenio from the Computer Unit, IFC, UNAM. References 1 Deng H Jasper H . Sexual dimorphism: how female cells win the race . Current Biology 2016 26 R212 – R21 5 . ( https://doi.org/10

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Britt J van Keulen Emma Children’s Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Pediatric Endocrinology, Amsterdam, The Netherlands

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Conor V Dolan Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands

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Bibian van der Voorn Department of Pediatric Endocrinology, Sophia Kinderziekenhuis, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

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Ruth Andrew Centre for Cardiovascular Science, University of Edinburgh, Queen’s Medical Research Institute, Edinburgh, UK

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Brian R Walker Centre for Cardiovascular Science, University of Edinburgh, Queen’s Medical Research Institute, Edinburgh, UK
Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK

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Hilleke Hulshoff Pol Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands

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Dorret I Boomsma Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands

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Joost Rotteveel Emma Children’s Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Pediatric Endocrinology, Amsterdam, The Netherlands

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Martijn J J Finken Emma Children’s Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Pediatric Endocrinology, Amsterdam, The Netherlands

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differences ( 5 , 6 , 7 , 8 , 9 , 10 ). Sexual dimorphism in HPA-axis activity has been suggested to be already present in early childhood. A recent meta-analysis suggested that boys and girls differed in basal HPA-axis activity, as assessed by salivary

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Sarmistha Banerjee Department of Biomedical Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA

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Allison M Hayes Department of Biomedical Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA

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Bernard H Shapiro Department of Biomedical Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA

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Introduction Sexual dimorphisms of some dozen or more hormone- and drug-metabolizing constituent cytochromes P450 (CYPs) observed in rats, humans, and many other species examined ( 1 ) are defined by two characteristics. (i) Following puberty

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Britt J van Keulen Department of Pediatric Endocrinology, Emma Children’s Hospital, Amsterdam University Medical Centers, location VUmc, Amsterdam, The Netherlands
Department of Pediatrics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Reproduction & Development Research Institute, de Boelelaan, Amsterdam, The Netherlands

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Michelle Romijn Department of Pediatric Endocrinology, Emma Children’s Hospital, Amsterdam University Medical Centers, location VUmc, Amsterdam, The Netherlands
Department of Pediatrics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Reproduction & Development Research Institute, de Boelelaan, Amsterdam, The Netherlands

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Bibian van der Voorn Department of Pediatric Endocrinology, Sophia Kinderziekenhuis, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

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Marita de Waard Emma Children’s Hospital, Amsterdam University Medical Centers, locations AMC and VUmc, Amsterdam, The Netherlands

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Michaela F Hartmann Steroid Research and Mass Spectrometry Unit, Laboratory for Translational Hormone Analytics, Pediatric Endocrinology & Diabetology, Center of Child and Adolescent Medicine, Justus-Liebig-University, Giessen, Germany

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Johannes B van Goudoever Emma Children’s Hospital, Amsterdam University Medical Centers, locations AMC and VUmc, Amsterdam, The Netherlands

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Stefan A Wudy Steroid Research and Mass Spectrometry Unit, Laboratory for Translational Hormone Analytics, Pediatric Endocrinology & Diabetology, Center of Child and Adolescent Medicine, Justus-Liebig-University, Giessen, Germany

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Joost Rotteveel Department of Pediatric Endocrinology, Emma Children’s Hospital, Amsterdam University Medical Centers, location VUmc, Amsterdam, The Netherlands

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Martijn J J Finken Department of Pediatric Endocrinology, Emma Children’s Hospital, Amsterdam University Medical Centers, location VUmc, Amsterdam, The Netherlands
Department of Pediatrics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Reproduction & Development Research Institute, de Boelelaan, Amsterdam, The Netherlands

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Objective

Sex-specific differences in hypothalamic–pituitary–adrenal axis activity might explain why male preterm infants are at higher risk of neonatal mortality and morbidity than their female counterparts. We examined whether male and female preterm infants differed in cortisol production and metabolism at 10 days post-partum.

Design and methods

This prospective study included 36 preterm born infants (18 boys) with a very low birth weight (VLBW) (<1.500 g). At 10 days postnatal age, urine was collected over a 4- to 6-h period. Glucocorticoid metabolites were measured using gas chromatography-mass spectrometry. Main outcome measures were: (1) cortisol excretion rate, (2) sum of all glucocorticoid metabolites, as an index of corticosteroid excretion rate, and (3) ratio of 11-OH/11-OXO metabolites, as an estimate of 11B-hydroxysteroid dehydrogenase (11B-HSD) activity. Differences between sexes, including interaction with Score of Neonatal Acute Physiology Perinatal Extension-II (SNAPPE II), sepsis and bronchopulmonary dysplasia (BPD), were assessed.

Results

No differences between sexes were found for cortisol excretion rate, corticosteroid excretion rate or 11B-HSD activity. Interaction was observed between: sex and SNAPPE II score on 11B-HSD activity (P = 0.04) and sex and BPD on cortisol excretion rate (P = 0.04).

Conclusion

This study did not provide evidence for sex-specific differences in adrenocortical function in preterm VLBW infants on a group level. However, in an interaction model, sex differences became manifest under stressful circumstances. These patterns might provide clues for the male disadvantage in neonatal mortality and morbidity following preterm birth. However, due to the small sample size, the data should be seen as hypothesis generating.

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Robert A Hart Centre for Bioactive Discovery in Health and Ageing, University of New England, Armidale, New South Wales, Australia

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Robin C Dobos NSW Department of Primary Industries, Armidale, New South Wales, Australia

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Linda L Agnew Centre for Bioactive Discovery in Health and Ageing, University of New England, Armidale, New South Wales, Australia

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Neil A Smart Centre for Bioactive Discovery in Health and Ageing, University of New England, Armidale, New South Wales, Australia

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James R McFarlane Centre for Bioactive Discovery in Health and Ageing, University of New England, Armidale, New South Wales, Australia

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comparable body condition, suggesting that there may be some sexual dimorphism in the roles it plays and possibly the tissues it targets. In women, leptin circulates at much higher concentrations with reports ranging from 40 to 300% higher than that found in

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Alessandro Ciresi Section of Endocrinology, Biomedical Department of Internal and Specialist Medicine (DIBIMIS), University of Palermo, Palermo, Italy

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Stefano Radellini Section of Endocrinology, Biomedical Department of Internal and Specialist Medicine (DIBIMIS), University of Palermo, Palermo, Italy

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Valentina Guarnotta Section of Endocrinology, Biomedical Department of Internal and Specialist Medicine (DIBIMIS), University of Palermo, Palermo, Italy

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Maria Grazia Mineo Section of Endocrinology, Biomedical Department of Internal and Specialist Medicine (DIBIMIS), University of Palermo, Palermo, Italy

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Carla Giordano Section of Endocrinology, Biomedical Department of Internal and Specialist Medicine (DIBIMIS), University of Palermo, Palermo, Italy

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Introduction The sexual dimorphism in the mechanisms involved in the regulation of somatotroph axis is well documented, and it might account for some of the sex differences in growth rate and body composition ( 1 ). Indeed, sex hormones are

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Maki Igarashi Medical Support Center for Japan Environmental and Children’s Study, National Center for Child Health and Development, Setagaya, Tokyo, Japan
Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Setagaya, Tokyo, Japan

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Tadayuki Ayabe Medical Support Center for Japan Environmental and Children’s Study, National Center for Child Health and Development, Setagaya, Tokyo, Japan
Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Setagaya, Tokyo, Japan

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Kiwako Yamamoto-Hanada Medical Support Center for Japan Environmental and Children’s Study, National Center for Child Health and Development, Setagaya, Tokyo, Japan

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Keiko Matsubara Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Setagaya, Tokyo, Japan

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Hatoko Sasaki Medical Support Center for Japan Environmental and Children’s Study, National Center for Child Health and Development, Setagaya, Tokyo, Japan

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Mayako Saito-Abe Medical Support Center for Japan Environmental and Children’s Study, National Center for Child Health and Development, Setagaya, Tokyo, Japan

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Miori Sato Medical Support Center for Japan Environmental and Children’s Study, National Center for Child Health and Development, Setagaya, Tokyo, Japan

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Nathan Mise Department of Environmental and Preventive Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan

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Akihiko Ikegami Department of Environmental and Preventive Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan

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Masayuki Shimono Regional Center for Pilot Study of Japan Environment and Children’s Study, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan

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Reiko Suga Regional Center for Pilot Study of Japan Environment and Children’s Study, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan

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Shouichi Ohga Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
Research Center for Environment and Developmental Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan

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Masafumi Sanefuji Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
Research Center for Environment and Developmental Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan

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Masako Oda Department of Public Health, Faculty of Life Sciences, Kumamoto University, Chuo-ku, Kumamoto, Japan

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Hiroshi Mitsubuchi Department of Neonatology, Kumamoto University Hospital, Chuo-ku, Kumamoto, Japan

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Takehiro Michikawa Japan Environment and Children’s Study Programme Office, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan

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Shin Yamazaki Japan Environment and Children’s Study Programme Office, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan

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Shoji Nakayama Japan Environment and Children’s Study Programme Office, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan

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Yukihiro Ohya Medical Support Center for Japan Environmental and Children’s Study, National Center for Child Health and Development, Setagaya, Tokyo, Japan

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Maki Fukami Medical Support Center for Japan Environmental and Children’s Study, National Center for Child Health and Development, Setagaya, Tokyo, Japan
Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Setagaya, Tokyo, Japan

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of age or later ( 1 , 4 , 5 , 6 ). Thus, sexual dimorphism in blood sex hormone levels is evident in children above 8 years of age. Furthermore, ultra-sensitive hormone assays using liquid chromatography-tandem mass spectrometry (LC-MS/MS) have

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Silvia Ciancia Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium

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Vanessa Dubois Basic and Translational Endocrinology (BaTE), Department of Basic and Applied Medical Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium

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Martine Cools Department of Internal Medicine and Pediatrics, Ghent University, Pediatric Endocrinology Service, Ghent University Hospital, Ghent, Belgium

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(In this review, we use the term ‘sex’ to refer to biological aspects of male or female development, whereas we use the term ‘gender’ to refer to an individual’s self-reported sense of gender.) differences before puberty, skeletal sexual dimorphism

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Nancy J Olsen Division of Rheumatology, Division of Endocrinology, Diabetes, and Metabolism, College of Medicine, Milton S Hershey Medical Center, The Pennsylvania State University, Mail Code H044, 500 University Drive, Hershey, Pennsylvania 17033-0850, USA

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Ann L Benko Division of Rheumatology, Division of Endocrinology, Diabetes, and Metabolism, College of Medicine, Milton S Hershey Medical Center, The Pennsylvania State University, Mail Code H044, 500 University Drive, Hershey, Pennsylvania 17033-0850, USA

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William J Kovacs Division of Rheumatology, Division of Endocrinology, Diabetes, and Metabolism, College of Medicine, Milton S Hershey Medical Center, The Pennsylvania State University, Mail Code H044, 500 University Drive, Hershey, Pennsylvania 17033-0850, USA

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have been proposed to account for the remarkable sexual dimorphism of most human autoimmune diseases (46) . The effects of X chromosomal genes (47, 48, 49) , the effects of Y chromosomal genes (50, 51, 52, 53) , fetal microchimerism in mothers (54

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Rafaella Sales de Freitas Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, Brazil

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Thiago F A França Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, Brazil

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Sabine Pompeia Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, Brazil

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inconsistencies may be related to the sexual dimorphism in kisspeptin expression, its serum concentrations, and the distribution of kisspeptin receptors, which are believed to explain some of the developmental differences between males and females ( 19 , 20

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