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Lina Lawenius Sahlgrenska Osteoporosis Centre and Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden

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Hannah Colldén Sahlgrenska Osteoporosis Centre and Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden

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Karin Horkeby Sahlgrenska Osteoporosis Centre and Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden

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Jianyao Wu Sahlgrenska Osteoporosis Centre and Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden

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Louise Grahnemo Sahlgrenska Osteoporosis Centre and Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden

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Liesbeth Vandenput Sahlgrenska Osteoporosis Centre and Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia

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Claes Ohlsson Sahlgrenska Osteoporosis Centre and Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden

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Klara Sjögren Sahlgrenska Osteoporosis Centre and Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden

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Studies in postmenopausal women and ovariectomized mice show that the probiotic mix Lacticaseibacillus paracasei DSM13434, Lactiplantibacillus plantarum DSM 15312 and DSM 15313 (L. Mix) can protect from bone loss caused by sex steroid deficiency. Whether probiotic bacteria can protect bone also in sex steroid-deficient males is less studied. We used the orchiectomized mouse as a model for age-dependent bone loss caused by decreasing sex hormone levels in males. We treated 10-week-old male mice with either vehicle (veh) or L. Mix for 6 weeks, starting 2 weeks before orchiectomy (orx) or sham surgery. Importantly, mice treated with L. Mix had a general increase in total body bone mineral density (BMD) and lean mass (P ≤ 0.05) compared with veh-treated mice. Detailed computer tomography analysis of dissected bones showed increased trabecular BMD of the distal metaphyseal region of the femur in L. Mix compared to veh-treated orx mice (+8.0%, P ≤ 0.05). In the vertebra, L. Mix treatment increased trabecular bone volume fraction BV/TV (+11.5%, P ≤ 0.05) compared to veh in orx mice. Also, L. Mix increased the levels of short-chain fatty acids (SCFAs) such as propionate and acetate and important intermediates in SCFA synthesis such as succinate and lactate in the cecal content of male mice. In conclusion, L. Mix treatment resulted in a general increase in BMD in adult male mice and prevented trabecular bone loss in femur and vertebra of orx mice. These bone protective effects of L. Mix were associated with increased levels of SCFAs in the cecal content of male mice.

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Laura L Gathercole Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK
Department of Biological and Medical Sciences, Oxford Brookes University, Oxford, UK

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Nikolaos Nikolaou Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK

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Shelley E Harris Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK

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Anastasia Arvaniti Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK
Department of Biological and Medical Sciences, Oxford Brookes University, Oxford, UK

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Toryn M Poolman Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK

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Jonathan M Hazlehurst Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK
Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK

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Denise V Kratschmar Swiss Centre for Applied Human Toxicology and Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland

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Marijana Todorčević Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK

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Ahmad Moolla Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK

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Niall Dempster Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK

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Ryan C Pink Department of Biological and Medical Sciences, Oxford Brookes University, Oxford, UK

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Michael F Saikali Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada

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Liz Bentley Mammalian Genetics Unit, Medical Research Council Harwell, Oxford, UK

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Trevor M Penning Center of Excellence in Environmental Toxicology, Department of Systems Pharmacology & Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA

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Claes Ohlsson Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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Carolyn L Cummins Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada

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Matti Poutanen Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, Turku, Finland

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Alex Odermatt Swiss Centre for Applied Human Toxicology and Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland

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Roger D Cox Mammalian Genetics Unit, Medical Research Council Harwell, Oxford, UK

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Jeremy W Tomlinson Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK

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Steroid 5β-reductase (AKR1D1) plays important role in hepatic bile acid synthesis and glucocorticoid clearance. Bile acids and glucocorticoids are potent metabolic regulators, but whether AKR1D1 controls metabolic phenotype in vivo is unknown. Akr1d1–/– mice were generated on a C57BL/6 background. Liquid chromatography/mass spectrometry, metabolomic and transcriptomic approaches were used to determine effects on glucocorticoid and bile acid homeostasis. Metabolic phenotypes including body weight and composition, lipid homeostasis, glucose tolerance and insulin tolerance were evaluated. Molecular changes were assessed by RNA-Seq and Western blotting. Male Akr1d1–/– mice were challenged with a high fat diet (60% kcal from fat) for 20 weeks. Akr1d1–/– mice had a sex-specific metabolic phenotype. At 30 weeks of age, male, but not female, Akr1d1–/– mice were more insulin tolerant and had reduced lipid accumulation in the liver and adipose tissue yet had hypertriglyceridemia and increased intramuscular triacylglycerol. This phenotype was associated with sexually dimorphic changes in bile acid metabolism and composition but without overt effects on circulating glucocorticoid levels or glucocorticoid-regulated gene expression in the liver. Male Akr1d1–/– mice were not protected against diet-induced obesity and insulin resistance. In conclusion, this study shows that AKR1D1 controls bile acid homeostasis in vivo and that altering its activity can affect insulin tolerance and lipid homeostasis in a sex-dependent manner.

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Nikshay Karthigan Cardiovascular Endocrinology Laboratory, Baker Heart and Diabetes Institute, Prahran, Australia
Endocrine Hypertension Group, Hudson Institute of Medical Research, Clayton, Australia

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Siobhan Lockwood Monash Cardiovascular Research Centre, Monash Health, Clayton, Australia
Department of Medicine, Monash University, Clayton, Australia

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Anthony White Monash Cardiovascular Research Centre, Monash Health, Clayton, Australia
Department of Medicine, Monash University, Clayton, Australia

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Jun Yang Endocrine Hypertension Group, Hudson Institute of Medical Research, Clayton, Australia
Department of Medicine, Monash University, Clayton, Australia

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Morag J Young Cardiovascular Endocrinology Laboratory, Baker Heart and Diabetes Institute, Prahran, Australia

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The mineralocorticoid receptor is a steroid hormone receptor that is well known for its involvement in fluid and electrolyte homeostasis in epithelial cells present in the distal nephron. The inappropriate activation of this receptor is now known to be implicated in various pathophysiological mechanisms in heart failure. Mineralocorticoid receptor antagonists offer substantial clinical benefit in patients with heart failure with reduced ejection fraction; however, for patients with heart failure with preserved ejection fraction, the treatment benefit is less clear. Biomarkers that can predict response to mineralocorticoid receptor antagonist treatment do not currently exist. Potential biomarkers may be modulated either directly by the mineralocorticoid receptor or indirectly via downstream effects and be able to reflect treatment outcomes, particularly changes in key parameters of cardiac health and function. A biomarker or set of biomarkers that can reliably predict responsiveness to mineralocorticoid receptor antagonist treatment at an early stage may allow for the selection of patients who are most likely to benefit from treatment thereby avoiding any unnecessary side effects associated with the use of these medications.

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Heleen I Jansen Endocrine Laboratory, Department of Clinical Chemistry, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Endocrine Laboratory, Department of Clinical Chemistry, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands

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Eveline Bruinstroop Department of Endocrinology & Metabolism, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

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Annemieke C Heijboer Endocrine Laboratory, Department of Clinical Chemistry, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Endocrine Laboratory, Department of Clinical Chemistry, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands

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Anita Boelen Endocrine Laboratory, Department of Clinical Chemistry, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

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Currently, thyroid hormone status is predominantly determined by the measurement of serum thyroid-stimulating hormone and free thyroxine. Although it is assumed that serum thyroid hormone (TH) concentrations within the reference range represent euthyroidism, it is unknown whether this reflects euthyroidism in all tissues (e.g. brain, muscle, bone and liver). To date, no serum marker has been established for clinical use that represents TH status within tissues accurately. However, several biomarkers have been investigated and innovative techniques have been used to unravel new biomarkers. This review provides an overview of proposed serum biomarkers that reflect tissue TH status in humans. Furthermore, we discuss the feasibility of these serum markers in clinical practice.

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Claire L Wood Division of Functional Genetics and Development, Roslin Institute, University of Edinburgh, Edinburgh, UK
Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK

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Rob van ‘t Hof Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK

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Scott Dillon Division of Functional Genetics and Development, Roslin Institute, University of Edinburgh, Edinburgh, UK

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Volker Straub John Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK

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Sze C Wong Developmental Endocrinology Research Group, School of Medicine, University of Glasgow, Glasgow, UK

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S Faisal Ahmed Developmental Endocrinology Research Group, School of Medicine, University of Glasgow, Glasgow, UK

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Colin Farquharson Division of Functional Genetics and Development, Roslin Institute, University of Edinburgh, Edinburgh, UK

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Short stature and osteoporosis are common in Duchenne muscular dystrophy (DMD) and its pathophysiology may include an abnormality of the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis, which is further exacerbated by long-term glucocorticoid (GC) treatment. Hence, an agent that has anabolic properties and may improve linear growth would be beneficial in this setting and therefore requires further exploration. A 5-week-old x-linked muscular dystrophy (mdx) mice were used as a model of DMD. They were treated with prednisolone ± GH + IGF-1 for 4 weeks and then compared to control mdx mice to allow the study of both growth and skeletal structure. GC reduced cortical bone area, bone fraction, tissue area and volume and cortical bone volume, as assessed by micro computed tomography (CT) In addition, GC caused somatic and skeletal growth retardation but improved grip strength. The addition of GH + IGF-1 therapy rescued the somatic growth retardation and induced additional improvements in grip strength (16.9% increase, P  < 0.05 compared to control). There was no improvement in bone microarchitecture (assessed by micro-CT and static histomorphometry) or biomechanical properties (assessed by three-point bending). Serum bone turnover markers (Serum procollagen 1 intact N-terminal propeptide (P1NP), alpha C-terminal telopeptide (αCTX)) also remained unaffected. Further work is needed to maximise these gains before proceeding to clinical trials in boys with DMD.

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Antonia Hufnagel University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Level 4, Addenbrooke’s Hospital, Cambridge, Cambridgeshire, UK

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Laura Dearden University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Level 4, Addenbrooke’s Hospital, Cambridge, Cambridgeshire, UK

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Denise S Fernandez-Twinn University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Level 4, Addenbrooke’s Hospital, Cambridge, Cambridgeshire, UK

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Susan E Ozanne University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Level 4, Addenbrooke’s Hospital, Cambridge, Cambridgeshire, UK

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Obesity and gestational diabetes during pregnancy have multiple short- and long-term consequences for both mother and child. One common feature of pregnancies complicated by maternal obesity and gestational diabetes is maternal hyperinsulinaemia, which has effects on the mother and her adaptation to pregnancy. Even though insulin does not cross the placenta insulin can act on the placenta as well affecting placental growth, angiogenesis and lipid metabolism. Obese and gestational diabetic pregnancies are often characterised by maternal hyperglycaemia resulting in exposure of the fetus to high levels of glucose, which freely crosses the placenta. This leads to stimulation of fetal ß-cells and insulin secretion in the fetus. Fetal hyperglycaemia/hyperinsulinaemia has been shown to cause multiple complications in fetal development, such as altered growth trajectories, impaired neuronal and cardiac development and early exhaustion of the pancreas. These changes could increase the susceptibility of the offspring to develop cardiometabolic diseases later in life. In this review, we aim to summarize and review the mechanisms by which maternal and fetal hyperinsulinaemia impact on (i) maternal health during pregnancy; (ii) placental and fetal development; (iii) offspring energy homeostasis and long-term cardiometabolic health; (iv) how interventions can alleviate these effects.

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Mohammad Reza Safarinejad Urology and Nephrology Research Center, Departments of Physical Medicine and Rehabilitation, Health and Community Medicine, Shahid Beheshti University (MC), Tehran, Iran

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Kamran Azma Urology and Nephrology Research Center, Departments of Physical Medicine and Rehabilitation, Health and Community Medicine, Shahid Beheshti University (MC), Tehran, Iran

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Ali Asgar Kolahi Urology and Nephrology Research Center, Departments of Physical Medicine and Rehabilitation, Health and Community Medicine, Shahid Beheshti University (MC), Tehran, Iran

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Karin L Gustafsson Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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Sofia Movérare-Skrtic Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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Helen H Farman Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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Cecilia Engdahl Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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Petra Henning Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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Karin H Nilsson Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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Julia M Scheffler Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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Edina Sehic Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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Ulrika Islander Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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Ellis Levin Division of Endocrinology, Department of Medicine, University of California, Irvine, Irvine, California, USA
Department of Veterans Affairs Medical Center, Long Beach, Long Beach, California, USA

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Claes Ohlsson Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
Department of Drug Treatment, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden

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Marie K Lagerquist Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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Selective estrogen receptor modulators (SERMs) act as estrogen receptor (ER) agonists or antagonists in a tissue-specific manner. ERs exert effects via nuclear actions but can also utilize membrane-initiated signaling pathways. To determine if membrane-initiated ERα (mERα) signaling affects SERM action in a tissue-specific manner, C451A mice, lacking mERα signaling due to a mutation at palmitoylation site C451, were treated with Lasofoxifene (Las), Bazedoxifene (Bza), or estradiol (E2), and various tissues were evaluated. Las and Bza treatment increased uterine weight to a similar extent in C451A and control mice, demonstrating mERα-independent uterine SERM effects, while the E2 effect on the uterus was predominantly mERα-dependent. Las and Bza treatment increased both trabecular and cortical bone mass in controls to a similar degree as E2, while both SERM and E2 treatment effects were absent in C451A mice. This demonstrates that SERM effects, similar to E2 effects, in the skeleton are mERα-dependent. Both Las and E2 treatment decreased thymus weight in controls, while neither treatment affected the thymus in C451A mice, demonstrating mERα-dependent SERM and E2 effects in this tissue. Interestingly, both SERM and E2 treatments decreased the total body fat percent in C451A mice, demonstrating the ability of these treatments to affect fat tissue in the absence of functional mERα signaling. In conclusion, mERα signaling can modulate SERM responses in a tissue-specific manner. This novel knowledge increases the understanding of the mechanisms behind SERM effects and may thereby facilitate the development of new improved SERMs.

Open access
Hiroyuki Enomoto Department of Anatomy and Neurobiology, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo, Japan
Department of Neurosurgery, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo, Japan

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Kinuyo Iwata Department of Anatomy and Neurobiology, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo, Japan

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Keisuke Matsumoto Department of Anatomy and Neurobiology, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo, Japan

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Mai Otsuka Department of Anatomy and Neurobiology, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo, Japan

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Akio Morita Department of Neurosurgery, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo, Japan

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Hitoshi Ozawa Department of Anatomy and Neurobiology, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo, Japan

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Kisspeptin neurons, i.e. KNDy neurons, in the arcuate nucleus (ARC) coexpress neurokinin B and dynorphin and regulate gonadotropin-releasing hormone/luteinizing hormone (LH) pulses. Because it remains unclear whether these neurons are associated with reproductive dysfunction in diabetic females, we examined the expression of KNDy neurons detected by histochemistry in streptozotocin (STZ)-induced diabetic female rats 8 weeks after STZ injection. We also evaluated relevant metabolic parameters – glucose, 3-hydroxybutyrate, and non-esterified fatty acids – as indicators of diabetes progression. Severe diabetes with hyperglycemia and severe ketosis suppressed the mRNA expression of KNDy neurons, resulting in low plasma LH levels and persistent diestrus. In moderate diabetes with hyperglycemia and moderate ketosis, kisspeptin-immunoreactive cells and plasma LH levels were decreased, while the mRNA expression of KNDy neurons remained unchanged. Mild diabetes with hyperglycemia and slight ketosis did not affect KNDy neurons and plasma LH levels. The number of KNDy cells was strongly and negatively correlated with plasma 3-hydroxybutyrate levels. The vaginal smear analysis showed unclear proestrus in diabetic rats 3–5 days after STZ injection, and the mRNA expression of kisspeptin in the ARC was decreased 2 weeks after STZ injection in severely diabetic rats. Kisspeptin neurons in the anteroventral periventricular nucleus (AVPV), which induce an LH surge, were unaffected at 2 and 8 weeks after STZ injection regardless of the diabetes severity. These results suggest that diabetes mellitus progression in females may negatively affect ARC kisspeptin neurons but not AVPV kisspeptin neurons, implicating a potential role of ARC kisspeptin neurons in menstrual disorder and infertility.

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Erica Yeo Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada
Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada

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Patricia L Brubaker Department of Physiology, University of Toronto, Toronto, ON, Canada
Department of Medicine, University of Toronto, Toronto, ON, Canada

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

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It is now well established that, beyond its role in nutrient processing and absorption, the intestine and its accompanying gut microbiome constitute a major site of immunological and endocrine regulation that mediates whole-body metabolism. Despite the growing field of host-microbe research, few studies explore what mechanisms govern this relationship in the context of pregnancy. During pregnancy, significant maternal metabolic adaptations are made to accommodate the additional energy demands of the developing fetus and to prevent adverse pregnancy outcomes. Recent data suggest that the maternal gut microbiota may play a role in these adaptations, but changes to maternal gut physiology and the underlying intestinal mechanisms remain unclear. In this review, we discuss selective aspects of intestinal physiology including the role of the incretin hormone, glucagon-like peptide 1 (GLP-1), and the role of the maternal gut microbiome in the maternal metabolic adaptations to pregnancy. Specifically, we discuss how bacterial components and metabolites could mediate the effects of the microbiota on host physiology, including nutrient absorption and GLP-1 secretion and action, and whether these mechanisms may change maternal insulin sensitivity and secretion during pregnancy. Finally, we discuss how these pathways could be altered in disease states during pregnancy including maternal obesity and diabetes.

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