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Patrycja A Jazwiec Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Canada
The Farncombe Family Digestive Diseases Research Institute, McMaster University, Hamilton, Canada

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Deborah M Sloboda Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Canada
The Farncombe Family Digestive Diseases Research Institute, McMaster University, Hamilton, Canada
Department of Pediatrics and Obstetrics and Gynecology, McMaster University, Hamilton, Canada

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environment ( Gluckman et al. 2005 , Hanson & Gluckman 2014 ). It has been proposed, however, that when a mismatch exists between the developmental and predicted postnatal environments, these adaptations may negatively affect health and result in increased

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Hironobu Kobayashi Department of Endocrinology and Metabolism, Division of Molecular and Cellular Adaptation, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan
Department of Breast and Endocrine Surgery, Nagoya University School of Medicine, Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
Second Department of Surgery, Nagoya University School of Medicine, Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

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Fukushi Kambe Department of Endocrinology and Metabolism, Division of Molecular and Cellular Adaptation, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan
Department of Breast and Endocrine Surgery, Nagoya University School of Medicine, Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
Second Department of Surgery, Nagoya University School of Medicine, Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

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Tsuneo Imai Department of Endocrinology and Metabolism, Division of Molecular and Cellular Adaptation, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan
Department of Breast and Endocrine Surgery, Nagoya University School of Medicine, Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
Second Department of Surgery, Nagoya University School of Medicine, Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

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Yatsuka Hibi Department of Endocrinology and Metabolism, Division of Molecular and Cellular Adaptation, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan
Department of Breast and Endocrine Surgery, Nagoya University School of Medicine, Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
Second Department of Surgery, Nagoya University School of Medicine, Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

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Toyone Kikumori Department of Endocrinology and Metabolism, Division of Molecular and Cellular Adaptation, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan
Department of Breast and Endocrine Surgery, Nagoya University School of Medicine, Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
Second Department of Surgery, Nagoya University School of Medicine, Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

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Sachiko Ohmori Department of Endocrinology and Metabolism, Division of Molecular and Cellular Adaptation, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan
Department of Breast and Endocrine Surgery, Nagoya University School of Medicine, Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
Second Department of Surgery, Nagoya University School of Medicine, Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

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Akimasa Nakao Department of Endocrinology and Metabolism, Division of Molecular and Cellular Adaptation, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan
Department of Breast and Endocrine Surgery, Nagoya University School of Medicine, Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
Second Department of Surgery, Nagoya University School of Medicine, Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

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Hisao Seo Department of Endocrinology and Metabolism, Division of Molecular and Cellular Adaptation, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan
Department of Breast and Endocrine Surgery, Nagoya University School of Medicine, Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
Second Department of Surgery, Nagoya University School of Medicine, Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

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An important role for the cyclin-dependent kinase inhibitors (CDKIs), p27Kip1 and p57Kip2, in the proliferation and differentiation of adrenal cells has been suggested by their knockout mice, which display adrenal hyperplasia. Adrenal development and function are primarily regulated by ACTH. In the present study, we investigated the effects of ACTH on the expression of p27Kip1, p57Kip2 and proliferating cell nuclear antigen (PCNA) in rat adrenals. Male Wistar rats were treated with dexametha-sone (Dex) to inhibit endogenous ACTH secretion. ACTH was then administered to the rats, and the adrenals were examined by Western blot and immunohisto-chemical analyses. Dex treatment induced shrinkage of adrenals where no PCNA-expressing cells were detected, but most of the cells expressed p27Kip1. Subsequent ACTH treatment resulted in the marked suppression of p27Kip1 expression, specifically in adrenocortical cells at 12 h after the stimulus. At 48 h, the p27Kip1 suppression still continued in the cortex, while the PCNA-expressing cells appeared mainly around the zona glomerulosa and increased at 72 h. At this time, the p27Kip1-expressing cells also appeared in the same zone. In contrast to p27Kip1, the expression of p57Kip2 was not detected in the Dex-treated adrenal. However, its expression was markedly induced by ACTH in the zona glomerulosa at 48 and 72 h. The results demonstrate that the primary site for mitogenic action of ACTH in rat adrenocortex is the zona glomerulosa, and that ACTH modulates proliferation of adrenocortical cells by regulating p27Kip1 and p57Kip2 expression in a time- and site-specific manner.

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Tracy Josephs Departments of Biochemistry and
Anatomy and Structural Biology, Otago School of Medical Sciences, University of Otago, PO Box 56, Dunedin 9054, New Zealand

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Hayley Waugh Departments of Biochemistry and
Anatomy and Structural Biology, Otago School of Medical Sciences, University of Otago, PO Box 56, Dunedin 9054, New Zealand

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Ilona Kokay Departments of Biochemistry and
Anatomy and Structural Biology, Otago School of Medical Sciences, University of Otago, PO Box 56, Dunedin 9054, New Zealand

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David Grattan Departments of Biochemistry and
Anatomy and Structural Biology, Otago School of Medical Sciences, University of Otago, PO Box 56, Dunedin 9054, New Zealand

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Mary Thompson Departments of Biochemistry and
Anatomy and Structural Biology, Otago School of Medical Sciences, University of Otago, PO Box 56, Dunedin 9054, New Zealand

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to alterations in pregnancy-related hormones, such as oestrogen, progesterone and prolactin, as potential mediators of insulin resistance in pregnancy. However, the effects of these hormones do not fully account for the metabolic adaptations that

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Helena A Walz Department of Experimental Medical Science, Biomedical Centre, C11, Lund University, SE-221 84 Lund, Sweden
Pulmonary/Critical-Care Medicine Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA
Department of Medical Physiology, the Panum Institute, DK-2200 Copenhagen, Denmark
Department of Clinical Sciences, Lund, Biomedical Centre, B11, Lund University, SE-221 84 Lund, Sweden

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Linda Härndahl Department of Experimental Medical Science, Biomedical Centre, C11, Lund University, SE-221 84 Lund, Sweden
Pulmonary/Critical-Care Medicine Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA
Department of Medical Physiology, the Panum Institute, DK-2200 Copenhagen, Denmark
Department of Clinical Sciences, Lund, Biomedical Centre, B11, Lund University, SE-221 84 Lund, Sweden

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Nils Wierup Department of Experimental Medical Science, Biomedical Centre, C11, Lund University, SE-221 84 Lund, Sweden
Pulmonary/Critical-Care Medicine Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA
Department of Medical Physiology, the Panum Institute, DK-2200 Copenhagen, Denmark
Department of Clinical Sciences, Lund, Biomedical Centre, B11, Lund University, SE-221 84 Lund, Sweden

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Emilia Zmuda-Trzebiatowska Department of Experimental Medical Science, Biomedical Centre, C11, Lund University, SE-221 84 Lund, Sweden
Pulmonary/Critical-Care Medicine Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA
Department of Medical Physiology, the Panum Institute, DK-2200 Copenhagen, Denmark
Department of Clinical Sciences, Lund, Biomedical Centre, B11, Lund University, SE-221 84 Lund, Sweden

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Fredrik Svennelid Department of Experimental Medical Science, Biomedical Centre, C11, Lund University, SE-221 84 Lund, Sweden
Pulmonary/Critical-Care Medicine Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA
Department of Medical Physiology, the Panum Institute, DK-2200 Copenhagen, Denmark
Department of Clinical Sciences, Lund, Biomedical Centre, B11, Lund University, SE-221 84 Lund, Sweden

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Vincent C Manganiello Department of Experimental Medical Science, Biomedical Centre, C11, Lund University, SE-221 84 Lund, Sweden
Pulmonary/Critical-Care Medicine Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA
Department of Medical Physiology, the Panum Institute, DK-2200 Copenhagen, Denmark
Department of Clinical Sciences, Lund, Biomedical Centre, B11, Lund University, SE-221 84 Lund, Sweden

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Thorkil Ploug Department of Experimental Medical Science, Biomedical Centre, C11, Lund University, SE-221 84 Lund, Sweden
Pulmonary/Critical-Care Medicine Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA
Department of Medical Physiology, the Panum Institute, DK-2200 Copenhagen, Denmark
Department of Clinical Sciences, Lund, Biomedical Centre, B11, Lund University, SE-221 84 Lund, Sweden

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Frank Sundler Department of Experimental Medical Science, Biomedical Centre, C11, Lund University, SE-221 84 Lund, Sweden
Pulmonary/Critical-Care Medicine Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA
Department of Medical Physiology, the Panum Institute, DK-2200 Copenhagen, Denmark
Department of Clinical Sciences, Lund, Biomedical Centre, B11, Lund University, SE-221 84 Lund, Sweden

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Eva Degerman Department of Experimental Medical Science, Biomedical Centre, C11, Lund University, SE-221 84 Lund, Sweden
Pulmonary/Critical-Care Medicine Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA
Department of Medical Physiology, the Panum Institute, DK-2200 Copenhagen, Denmark
Department of Clinical Sciences, Lund, Biomedical Centre, B11, Lund University, SE-221 84 Lund, Sweden

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Bo Ahrén Department of Experimental Medical Science, Biomedical Centre, C11, Lund University, SE-221 84 Lund, Sweden
Pulmonary/Critical-Care Medicine Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA
Department of Medical Physiology, the Panum Institute, DK-2200 Copenhagen, Denmark
Department of Clinical Sciences, Lund, Biomedical Centre, B11, Lund University, SE-221 84 Lund, Sweden

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Lena Stenson Holst Department of Experimental Medical Science, Biomedical Centre, C11, Lund University, SE-221 84 Lund, Sweden
Pulmonary/Critical-Care Medicine Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA
Department of Medical Physiology, the Panum Institute, DK-2200 Copenhagen, Denmark
Department of Clinical Sciences, Lund, Biomedical Centre, B11, Lund University, SE-221 84 Lund, Sweden

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because of defective islet adaptation that glucose intolerance develops in type 2 diabetes ( Ahrén & Pacini 2005 ). The mechanism responsible for islet adaptation has not been fully established. In this study we used the RIP-PDE3B/2 mice to explore

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Harleen Kaur Robinson Research Institute, University of Adelaide, Adelaide, Australia
Adelaide Medical School, University of Adelaide, Adelaide, Australia

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Beverly S Muhlhausler CSIRO Nutrition and Health, Adelaide, Australia

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Claire T Roberts Robinson Research Institute, University of Adelaide, Adelaide, Australia
Adelaide Medical School, University of Adelaide, Adelaide, Australia
College of Medicine and Public Health, Flinders University, Bedford Park, South Australia, Australia
College of Medicine and Public Health, Flinders University, Bedford Park, South Australia, Australia

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Kathryn L Gatford Robinson Research Institute, University of Adelaide, Adelaide, Australia
Adelaide Medical School, University of Adelaide, Adelaide, Australia

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review. Circulating levels of GH and IGF1 change markedly in pregnancy, and new information is emerging on how this axis contributes to maternal adaptation to pregnancy, fetal–placental growth and development, particularly in humans and rodents. Exogenous

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J Han The Research Institute for Children, Department of Pediatrics, Children's Hospital at New Orleans, 200 Henry Clay Avenue, New Orleans, Louisiana 70118, USA

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Y Q Liu The Research Institute for Children, Department of Pediatrics, Children's Hospital at New Orleans, 200 Henry Clay Avenue, New Orleans, Louisiana 70118, USA
The Research Institute for Children, Department of Pediatrics, Children's Hospital at New Orleans, 200 Henry Clay Avenue, New Orleans, Louisiana 70118, USA

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-cell adaptation and insulin secretion. Inhibition of PC with its inhibitor phenylacetic acid (PAA) prevents glucose-stimulated insulin secretion (GSIS; Farfari et al . 2000 , Liu et al . 2002 , 2005 ). We found that PAA also reduces the β-cell proliferation

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Victoria Diedrich Institute of Neurobiology, Ulm University, Ulm, Germany

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Elena Haugg Institute of Neurobiology, Ulm University, Ulm, Germany

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Carola Dreier Institute of Neurobiology, Ulm University, Ulm, Germany

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Annika Herwig Institute of Neurobiology, Ulm University, Ulm, Germany

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bottlenecks caused by their variable surroundings. Seasonal adaptations include fur changes, readjustment of thermoregulatory capacity and metabolism, precise timing of reproduction as well as pronounced annual body weight cycles and all contribute to one goal

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Francesca Spiga
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Louise R Harrison
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Cliona P MacSweeney Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, Department of Molecular Pharmacology, University of Bristol, Dorothy Hodgkin Building, Whitson Street, BS1 3NY Bristol, UK

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Fiona J Thomson Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, Department of Molecular Pharmacology, University of Bristol, Dorothy Hodgkin Building, Whitson Street, BS1 3NY Bristol, UK

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Mark Craighead Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, Department of Molecular Pharmacology, University of Bristol, Dorothy Hodgkin Building, Whitson Street, BS1 3NY Bristol, UK

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Stafford L Lightman
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– 1124 . Chen X Herbert J 1995 Regional changes in c-fos expression in the basal forebrain and brainstem during adaptation to repeated stress: correlations with cardiovascular, hypothermic and endocrine responses . Neuroscience 64 675 – 685

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Thomas G Hill Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, Churchill Hospital, University of Oxford, Oxford, UK

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Lorna I F Smith Diabetes Research Group, School of Cardiovascular and Metabolic Medicine and Sciences, King’s College London, London, UK

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Inmaculada Ruz-Maldonado Department of Internal Medicine (Endocrinology), Yale University, New Haven, Connecticut, USA

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Peter M Jones Diabetes Research Group, School of Cardiovascular and Metabolic Medicine and Sciences, King’s College London, London, UK

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James E Bowe Diabetes Research Group, School of Cardiovascular and Metabolic Medicine and Sciences, King’s College London, London, UK

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and pro-survival adaptations through autocrine/paracrine signalling ( Kim et al. 2010 , Schraenen et al. 2010 , Ohara-Imaizumi et al. 2013 , Almaca et al. 2016 , Moon et al. 2020 ). In addition to the established role of the lactogenic

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Richard A Ehrhardt Departments of Animal Science and Large Animal Clinical Sciences, Michigan State University, East Lansing, Michigan, USA

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Andreas Foskolos Institute of Biological, Environmental and Rural Sciences, Aberystwyth University, Aberystwyth, UK

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Sarah L Giesy Department of Animal Science, Cornell University, Ithaca, New York, USA

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Stephanie R Wesolowski University of Colorado School of Medicine, Aurora, Colorado, USA

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Christopher S Krumm Department of Animal Science, Cornell University, Ithaca, New York, USA

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W Ronald Butler Department of Animal Science, Cornell University, Ithaca, New York, USA

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Susan M Quirk Department of Animal Science, Cornell University, Ithaca, New York, USA

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Matthew R Waldron Department of Animal Science, Cornell University, Ithaca, New York, USA

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Yves R Boisclair Department of Animal Science, Cornell University, Ithaca, New York, USA

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adaptive metabolism in the context of lactation. Adaptive metabolism is hormonally regulated as illustrated by adaptations triggered in early lactating dairy cows by interactions among insulin, growth hormone (GH), and insulin-like growth factor (IGF)1

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