DOCSLIB.ORG

Nicotinic Signalling and Neurosteroid Modulation in Principal Neurons of the Hippocampal Formation and Prefrontal Cortex

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Nicotinic Signalling and Neurosteroid Modulation in Principal Neurons of the Hippocampal Formation and Prefrontal Cortex Nicotinic Signalling and Neurosteroid Modulation in Principal Neurons of the Hippocampal Formation and Prefrontal Cortex by Beryl Yik Ting Chung A Thesis presented to The University of Guelph In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biomedical Sciences and Neuroscience Guelph, Ontario, Canada © Beryl Yik Ting Chung, April, 2018 ABSTRACT NICOTINIC SIGNALLING AND NEUROSTEROID MODULATION IN PRINCIPAL NEURONS OF THE HIPPOCAMPAL FORMATION AND PREFRONTAL CORTEX Beryl Yik Ting Chung Advisor: University of Guelph, 2018 Dr. Craig D.C. Bailey Nicotinic signalling plays an important role in coordinating the response of neuronal networks in many brain regions. During pre- and postnatal circuit formation, neurotransmission mediated by nicotinic acetylcholine receptors (nAChRs) influences neuronal survival and regulates neuronal excitability, synaptic transmission, and synaptic plasticity. Nicotinic signalling is also necessary for the proper function of the hippocampal formation (HF) and prefrontal cortex (PFC), which are anatomically and functionally connected and facilitate higher-order cognitive functions. The decline or dysfunction in nicotinic signalling and nAChR function has been observed in various neurological disorders, and the disruption or alteration of nicotinic signalling in the HF and/or PFC can impair learning and memory. While the location and functional role of the α4β2* nAChR isoform has been well characterized in the medial portion of the PFC, this is not well-established in the HF. What is the role of α4β2* nAChRs in excitatory principal neurons of the HF during early development? Growing evidence suggests that the progesterone metabolite allopregnanolone (ALLO) plays a role in mediating the proper function of the HF and the PFC, and that it may also inhibit nAChR function. How might ALLO influence α4β2* nAChR function during early development and/or affect neuronal excitation within a living system? This thesis aims to develop a foundation towards understanding the role of α4β2* nAChR-mediated neurotransmission in principal neurons of the HF during development, and the role of ALLO in modulating α4β2* nicotinic receptor function during this period. In this thesis, I demonstrate that functional ⍺4β2* nAChRs are present in principal neurons of the developing mouse HF. The function of these receptors is developmentally regulated, and nicotinic excitation differs between male and female mice. I also demonstrate that ALLO negatively modulates α4β2* nAChR function in living neurons. I show for the first time that crosstalk between the membrane progesterone receptor complex and the nAChR likely facilitates the actions of ALLO to modulate nAChR function. The findings in this thesis present new insights on ⍺4β2* nAChR expression and function, while adding to our understanding of how these receptors may influence neuronal excitability, synaptic transmission, and synaptic plasticity during early development. iv ACKNOWLEDGEMENTS The work presented in this thesis not only reflects a milestone in my long-term interest in biomedical sciences, but also the product of those who have continuously supported me during the term of my candidature. First and foremost, I wish to thank my advisor, Dr. Craig Bailey. I am most grateful for your guidance and support, your tremendous patience, and faith in my capabilities as I developed as a researcher. I would also like to thank Warren Bignell for giving me the strongest foundation I could ask for, and ‘members of the Bailey Lab’, for your friendship and wise advice on everything. I would like to express my sincere appreciation for my advisory committee: Dr. Elena Choleris for her encouraging words and feedback; Dr. Brad Hanna for instilling in me the importance of practicing sound science; and Dr. Neil MacLusky for the numerous opportunities and reminders that I am capable of more than I know. I would like to thank my friends and family for your unconditional support despite my confusing role as a graduate student. To my mom and dad, I thank you for the opportunity that you have given me to unreservedly pursue and achieve my goals and aspirations. I hope that my work now and future milestones will continue to make you proud. To my sister, thank you for allowing me to exercise the perks of being the malicious older sibling and inspiring me to be a better person each day. Finally, thank you Calvin, for your unparalleled patience with my frenzy and the comfort that you have given me during the many long days and nights of this journey. v DECLARATION OF WORK PERFORMED I declare that I have performed all the work presented in this thesis except for the following: Electrophysiological recordings in Chapter 2 were in part completed by Warren Bignell and Derek Jacklin. vi TABLE OF CONTENTS ABSTRACT ....................................................................................................................... ii ACKNOWLEDGEMENTS ............................................................................................ iv DECLARATION OF WORK PERFORMED ............................................................... v TABLE OF CONTENTS ................................................................................................ vi LIST OF TABLES ............................................................................................................ x LIST OF FIGURES ......................................................................................................... xi LIST OF ABBREVIATIONS ....................................................................................... xiii CHAPTER 1: GENERAL INTRODUCTION .......................................................... 1-48 1.1 ROLE OF THE HIPPOCAMPAL FORMATION AND PREFRONTAL CORTEX IN HIGHER-ORDER COGNITIVE FUNCTIONS ............................................................................. 2 1.1.1 Anatomical organization of the hippocampal formation .................................... 4 1.1.2 Anatomical organization of the prefrontal cortex ............................................... 8 1.1.3 Functional interaction between the hippocampal formation and prefrontal cortex .......................................................................................................................... 10 1.2 NICOTINIC ACETYLCHOLINE RECEPTORS IN THE HIPPOCAMPAL FORMATION AND PREFRONTAL CORTEX ..................................................................................................... 14 1.2.1 Nicotinic receptor composition and isoforms ................................................... 16 1.2.2 Nicotinic signalling in the hippocampal formation .......................................... 19 1.2.3 Nicotinic signalling in the prefrontal cortex ..................................................... 24 1.2.4 Sex differences in nicotinic signalling ............................................................... 29 1.3 MODULATION OF BRAIN FUNCTION BY THE PROGESTERONE METABOLITE ALLOPREGNANOLONE ..................................................................................................... 32 1.3.1 The de novo production of progesterone and its metabolites within the brain . 33 1.3.2 Allopregnanolone in the hippocampal formation and prefrontal cortex .......... 36 1.3.3 Non-classical progesterone receptors: membrane progesterone receptor and the progesterone membrane receptor component ............................................................ 38 1.3.4 Neurosteroid modulation of ligand gated ion channel receptors ..................... 42 1.4 THESIS RATIONALE AND APPROACH .......................................................................... 44 CHAPTER 2: FUNCTIONAL HETEROMERIC 42* NICOTINIC ACETYLCHOLINE RECEPTOR IN DEVELOPING MOUSE HIPPOCAMPUS CA1 PRINCIPAL NEURONS ...................................................................................................................................... 49-85 2.1 ABSTRACT ................................................................................................................ 50 2.2 INTRODUCTION ......................................................................................................... 50 2.3 MATERIALS AND METHODS ...................................................................................... 53 2.3.1 Experimental Animals ....................................................................................... 53 2.3.2 Electrophysiology .............................................................................................. 54 vii 2.3.3 Neuron Morphology ......................................................................................... 57 2.3.4 Statistical Analysis ........................................................................................... 58 2.4 RESULTS ................................................................................................................... 59 2.4.1 Excitation of young postnatal CA1 pyramidal neurons by postsynaptic heteromeric nicotinic receptors ................................................................................ 59 2.4.2 Nicotine desensitization of nicotinic receptors in young postnatal CA1 pyramidal neurons..................................................................................................... 64 2.4.3 Developmental changes to nicotinic receptor function ..................................... 67 2.4.4 Influence of endogenous acetylcholinesterase and extracellular matrix density on observed developmental changes to CA1
Load more

Recommended publications
  • Original Article 4-Hydroxy Estrogen Metabolite, Causing Genomic
    Am J Transl Res 2019;11(8):4992-5007 www.ajtr.org /ISSN:1943-8141/AJTR0096694 Original Article 4-Hydroxy estrogen metabolite, causing genomic instability by attenuating the function of spindle-assembly checkpoint, can serve as a biomarker for breast cancer Suyu Miao1,2*, Fengming Yang1*, Ying Wang2*, Chuchu Shao1, David T Zava3, Qiang Ding2, Yuenian Eric Shi1 1Department of Oncology, 2Jiangsu Breast Disease Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, China; 3ZRT Laboratory, Beaverton 97003, USA. *Equal contributors. Received May 8, 2019; Accepted July 17, 2019; Epub August 15, 2019; Published August 30, 2019 Abstract: Sex hormone metabolism is altered during mammary gland tumorigenesis, and different metabolites may have different effects on mammary epithelial cells. This study aimed to evaluate associations between urinary sexual metabolite levels and breast cancer risk among premenopausal women of Mainland China. The molecular metabolism of the cancer-related metabolites was also explored based on the clinical data. The sex hormone me- tabolites in the urine samples of patients with breast cancer versus normal healthy women were analyzed com- prehensively. Among many alterations of sex hormone metabolisms, 4-hydroxy estrogen (4-OH-E) metabolite was found to be significantly increased in the urine samples of patients with breast cancer compared with the normal healthy controls. This was the most important risk factor for breast cancer. Several experiments were conducted in vitro and in vivo to probe this mechanism. 4-Hydroxyestradiol (4-OH-E2) was found to induce malignant transforma- tion of breast cells and tumorigenesis in nude mice. At the molecular level, 4-OH-E2 compromised the function of spindle-assembly checkpoint and rendered resistance to the anti-microtubule drug.
    [Show full text]
  • Peripheral Nervous System……………………………………………….9
    PhD School in Integrative Biomedical Research Department of Pharmacological and Biomolecular Sciences Curriculum: Neuroscience Molecular basis for the development of innovative therapies for peripheral neuropathies treatment: role and cross-regulation of the GABAergic system and neuroactive steroids SDD BIO/09 - Physiology Luca Franco Castelnovo Badge number R10402 PhD Tutor: Prof. Valerio Magnaghi PhD School Coordinator: Prof. Chiarella Sforza Academic year 2015/2016 INDEX Abstract…………………………………………………………………...page 1 Abbreviations list…………………………………………………………….....5 Introduction………………………………………………………………….....8 Peripheral nervous system……………………………………………….9 General concepts……………...……….……………………………........……..9 Sensory system and nociceptive fibers.………………..………….…………..12 Schwann cells and myelination……….……..………………...………………15 Peripheral neuropathies…….…………………………………………...26 General concepts……………………………………………………...……….26 Neuropathic pain……………………………………...……………………….27 Nerve regeneration…………………………………………………………….28 The GABAergic system………….……………………………………...32 GABA……………….…………………………………………………..……..32 GABA-A receptors…………………………………………………………….33 GABA-B receptors…………………………………………………………….42 GABAergic system in the peripheral nervous system…………………………47 Protein kinase C – type ε……………………….………………………..51 General concepts…………………………………………………….…………51 Cross-talk with allopregnanolone and GABA-A………………………………54 Neuroactive steroids…………......………………………………………57 General concepts…………………………………….…………………………57 Mechanism of action…………………………….……………………………..59 Progesterone derivatives………………………………….……………………60
    [Show full text]
  • Progesterone 7K77 49-3265/R3 B7K770 Read Highlighted Changes Revised April, 2010 Progesterone
    en system Progesterone 7K77 49-3265/R3 B7K770 Read Highlighted Changes Revised April, 2010 Progesterone Customer Service: Contact your local representative or find country specific contact information on www.abbottdiagnostics.com Package insert instructions must be carefully followed. Reliability of assay results cannot be guaranteed if there are any deviations from the instructions in this package insert. Key to symbols used List Number Calibrator (1,2) In Vitro Diagnostic Medical Control Low, Medium, High Device (L, M, H) Lot Number Reagent Lot Expiration Date Reaction Vessels Serial Number Sample Cups Septum Store at 2-8°C Replacement Caps Consult instructions for use Warning: May cause an allergic reaction Contains sodium azide. Contact Manufacturer with acids liberates very toxic gas. See REAGENTS section for a full explanation of symbols used in reagent component naming. 1 NAME REAGENTS ARCHITECT Progesterone Reagent Kit, 100 Tests INTENDED USE NOTE: Some kit sizes are not available in all countries or for use on all ARCHITECT i Systems. Please contact your local distributor. The ARCHITECT Progesterone assay is a Chemiluminescent Microparticle Immunoassay (CMIA) for the quantitative determination of progesterone in ARCHITECT Progesterone Reagent Kit (7K77) human serum and plasma. • 1 or 4 Bottle(s) (6.6 mL) Anti-fluorescein (mouse, monoclonal) fluorescein progesterone complex coated Microparticles SUMMARY AND EXPLANATION OF TEST in TRIS buffer with protein (bovine and murine) and surfactant Progesterone is produced primarily by the corpus luteum of the ovary stabilizers. Concentration: 0.1% solids. Preservatives: sodium azide in normally menstruating women and to a lesser extent by the adrenal and ProClin. cortex.1 At approximately the 6th week of pregnancy, the placenta 2-5 • 1 or 4 Bottle(s) (17.0 mL) Anti-progesterone (sheep, becomes the major producer of progesterone.
    [Show full text]
  • Neurosteroids in Depression: a Review 39
    PDF hosted at the Radboud Repository of the Radboud University Nijmegen The following full text is a publisher's version. For additional information about this publication click this link. http://hdl.handle.net/2066/71267 Please be advised that this information was generated on 2021-09-26 and may be subject to change. Frank van Broekhoven Effects of progesterone and allopregnanolone on stress, attention, cognition and mood | Frank van Broekhoven ISBN 978-90-9023655-1 Copyright ©2008 Frank van Broekhoven. The copyright of articles that have already been published has been transferred to the respective journals. No part of this book may be reproduced, in any form, without prior written permission from the author. Niets uit deze uitgave mag worden verveelvoudigd en/of openbaar gemaakt in welke vorm dan ook, zonder voorafgaande schriftelijke toestemming van de auteur. Coverdesign and layout by: Communicatie Kant, Dinxperlo, The Netherlands Printed by: Up2data, Bocholt, Germany The financial support for the printing of this thesis by Eli Lilly Nederland BV, Janssen-Cilag BV, the Department of Psychiatry from the Radboud University Nijmegen Medical Centre, and Karakter, Child and Adolescent Psy- chiatry University Centre, Nijmegen, is gratefully acknowledged. Effects of progesterone and allopregnanolone on stress, attention, cognition and mood Een wetenschappelijke proeve op het gebied van de Medische Wetenschappen Proefschrift ter verkrijging van de graad van doctor aan de Radboud Universiteit Nijmegen op gezag van de rector magnificus prof. mr. S.C.J.J. Kortmann, volgens besluit van het College van Decanen in het openbaar te verdedigen op maandag 24 november 2008 om 15.30 uur precies door Frank van Broekhoven geboren op 8 december 1969 te Groenlo Promotores: prof.
    [Show full text]
  • PRODUCT SPECIFICATION Anti-PAQR9 Product
    Anti-PAQR9 Product Datasheet Polyclonal Antibody PRODUCT SPECIFICATION Product Name Anti-PAQR9 Product Number HPA052798 Gene Description progestin and adipoQ receptor family member IX Clonality Polyclonal Isotype IgG Host Rabbit Antigen Sequence Recombinant Protein Epitope Signature Tag (PrEST) antigen sequence: IMLESWLFDLRGENPTLFVHF Purification Method Affinity purified using the PrEST antigen as affinity ligand Verified Species Human Reactivity Recommended IHC (Immunohistochemistry) Applications - Antibody dilution: 1:20 - 1:50 - Retrieval method: HIER pH6 Characterization Data Available at atlasantibodies.com/products/HPA052798 Buffer 40% glycerol and PBS (pH 7.2). 0.02% sodium azide is added as preservative. Concentration Lot dependent Storage Store at +4°C for short term storage. Long time storage is recommended at -20°C. Notes Gently mix before use. Optimal concentrations and conditions for each application should be determined by the user. For protocols, additional product information, such as images and references, see atlasantibodies.com. Product of Sweden. For research use only. Not intended for pharmaceutical development, diagnostic, therapeutic or any in vivo use. No products from Atlas Antibodies may be resold, modified for resale or used to manufacture commercial products without prior written approval from Atlas Antibodies AB. Warranty: The products supplied by Atlas Antibodies are warranted to meet stated product specifications and to conform to label descriptions when used and stored properly. Unless otherwise stated, this warranty is limited to one year from date of sales for products used, handled and stored according to Atlas Antibodies AB's instructions. Atlas Antibodies AB's sole liability is limited to replacement of the product or refund of the purchase price.
    [Show full text]
  • Multidisciplinary Analysis of Biological Effects of Novel Analogs of The
    UNIVERSITÉ DE STRASBOURG ÉCOLE DOCTORALE des Sciences de la vie et de la santé (ED 414) INSERM UMR_S U1119 Biopathologies de la Myéline, Neuroprotection et Stratégies Thérapeutiques THÈSE En cotutelle avec l´Albert-Ludwigs-Universität Freiburg, Allemagne présentée par : Mona KAROUT soutenue le : 30 Septembre 2015 pour obtenir le grade de : Docteur de l’université de Strasbourg Discipline / Spécialité : Neurosciences Multidisciplinary analysis of biological effects of novel analogs of the neurosteroid allopregnanolone: evidence for a proliferative, neurogenic and ne uroprote ctive action THÈSE dirigée par : M. MENSAH-NYAGAN Ayikoé, Guy Professeur, Université de Strasbourg, France M. HOFMANN Hans-Dieter Professeur, Albert-Ludwigs-Universität Freiburg, Allemagne RAPPORTEURS : M. FISCHBACH Karl-Friedrich Professeur, Albert-Ludwigs-Universität Freiburg, Allemagne M. SCHWEMMLE Martin Professeur, Albert-Ludwigs-Universität Freiburg, Allemagne AUTRES MEMBRES DU JURY : M. DUFOUR André Professeur, Université de Strasbourg, France Mme. PATTE-MENSAH Christine Docteur, Université de Strasbourg, France !"# $%&'(%# To my parents A mes parents Acknowledgement ACKNOWLEDGEMENT First of all, I would like to express my appreciation and gratitude to all members of my thesis committee, Prof. Karl-Friedrich Fischbach, Prof. Martin Schwemmle, Prof. André Dufour and Dr. Christine Patte-Mensah for taking the time to evaluate my thesis. Furthermore, I would like to express my deepest gratitude to my two PhD supervisors Prof. Ayikoé Guy Mensah-Nyagan and Prof. Hans-Dieter Hofmann. I am very thankful to you Prof. Mensah-Nyagan for giving me a great opportunity for performing this joint French-German PhD. Thank you very much for the continuous support, for your patience, enthusiasm, passion for research and immense knowledge.
    [Show full text]
  • BMC Evolutionary Biology Biomed Central
    BMC Evolutionary Biology BioMed Central Research article Open Access Evolution of pharmacologic specificity in the pregnane X receptor Sean Ekins1,2,3, Erica J Reschly4, Lee R Hagey5 and Matthew D Krasowski*4 Address: 1Collaborations in Chemistry, Inc., Jenkintown, PA, USA, 2Department of Pharmaceutical Sciences, University of Maryland, Baltimore, MD, USA, 3Department of Pharmacology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ, USA, 4Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA and 5Department of Medicine, University of California at San Diego, San Diego, CA, USA Email: Sean Ekins - [email protected]; Erica J Reschly - [email protected]; Lee R Hagey - [email protected]; Matthew D Krasowski* - [email protected] * Corresponding author Published: 2 April 2008 Received: 28 August 2007 Accepted: 2 April 2008 BMC Evolutionary Biology 2008, 8:103 doi:10.1186/1471-2148-8-103 This article is available from: http://www.biomedcentral.com/1471-2148/8/103 © 2008 Ekins et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: The pregnane X receptor (PXR) shows the highest degree of cross-species sequence diversity of any of the vertebrate nuclear hormone receptors. In this study, we determined the pharmacophores for activation of human, mouse, rat, rabbit, chicken, and zebrafish PXRs, using a common set of sixteen ligands. In addition, we compared in detail the selectivity of human and zebrafish PXRs for steroidal compounds and xenobiotics.
    [Show full text]
  • Tissue Steroid Levels in Response to Reduced Testicular Estrogen Synthesis in the Male Pig, Sus
    1 Tissue steroid levels in response to reduced testicular estrogen synthesis in the male pig, Sus 2 scrofa 3 Heidi Kucera1, Birgit Puschner1, Alan Conley2, Trish Berger3* 4 5 1 Department of Molecular Biosciences, School of Veterinary Medicine, University of California, 6 Davis, CA 7 2 Department of Population Health and Reproduction, School of Veterinary Medicine, University 8 of California, Davis, CA 9 3 Department of Animal Science, College of Agricultural and Environmental Sciences, 10 University of California, Davis, CA 11 12 Short title: Estrogen sulfates, aromatase activity and free estrogen concentrations in prostate, 13 testis and liver 14 15 * Corresponding author 16 E-mail: [email protected] (TB) 17 1 18 Abstract 19 Production of steroid hormones is complex and dependent upon steroidogenic enzymes, 20 cofactors, receptors, and transporters expressed within a tissue. Collectively, these factors create 21 an environment for tissue-specific steroid hormone profiles and potentially tissue-specific 22 responses to drug administration. Our objective was to assess steroid production, including 23 sulfated steroid metabolites in the boar testis, prostate, and liver following inhibition of 24 aromatase, the enzyme that converts androgen precursors to estrogens. Boars were treated with 25 the aromatase inhibitor, letrozole from 11 to 16 weeks of age and littermate boars received the 26 canola oil vehicle. Steroid profiles were evaluated in testes, prostate, and livers of 16, 20, and 40 27 week old boars using liquid chromatography/mass spectrometry. Testis, prostate, and liver had 28 unique steroid profiles in vehicle-treated animals. Only C18 steroid hormones were altered by 29 treatment with the aromatase inhibitor, letrozole; no significant differences were detected in any 30 of the C19 or C21 steroids evaluated.
    [Show full text]
  • Proteomic and Metabolomic Analyses of Biological Systems with Liquid Chromatography Tandem Mass Spectrometry and Ion Mobility Mass Spectrometry
    Graduate Theses, Dissertations, and Problem Reports 2017 Proteomic and Metabolomic Analyses of Biological Systems with Liquid Chromatography Tandem Mass Spectrometry and Ion Mobility Mass Spectrometry Megan M. Maurer Follow this and additional works at: https://researchrepository.wvu.edu/etd Recommended Citation Maurer, Megan M., "Proteomic and Metabolomic Analyses of Biological Systems with Liquid Chromatography Tandem Mass Spectrometry and Ion Mobility Mass Spectrometry" (2017). Graduate Theses, Dissertations, and Problem Reports. 6179. https://researchrepository.wvu.edu/etd/6179 This Dissertation is protected by copyright and/or related rights. It has been brought to you by the The Research Repository @ WVU with permission from the rights-holder(s). You are free to use this Dissertation in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you must obtain permission from the rights-holder(s) directly, unless additional rights are indicated by a Creative Commons license in the record and/ or on the work itself. This Dissertation has been accepted for inclusion in WVU Graduate Theses, Dissertations, and Problem Reports collection by an authorized administrator of The Research Repository @ WVU. For more information, please contact [email protected]. Proteomic and Metabolomic Analyses of Biological Systems with Liquid Chromatography Tandem Mass Spectrometry and Ion Mobility Mass Spectrometry Megan M. Maurer Dissertation submitted to the Eberly College of Arts and Sciences at West Virginia University in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Analytical Chemistry Stephen J. Valentine, Ph.D., Chair Suzanne Bell, Ph.D. Glen P. Jackson, Ph.D.
    [Show full text]
  • The Steroid Metabolome in Women with Premenstrual Dysphoric Disorder During Gnrh Agonist-Induced Ovarian Suppression: Effects of Estradiol and Progesterone Addback
    CORE Metadata, citation and similar papers at core.ac.uk Provided by Carolina Digital Repository OPEN Citation: Transl Psychiatry (2017) 7, e1193; doi:10.1038/tp.2017.146 www.nature.com/tp ORIGINAL ARTICLE The steroid metabolome in women with premenstrual dysphoric disorder during GnRH agonist-induced ovarian suppression: effects of estradiol and progesterone addback TV Nguyen1,2,10, JM Reuter1,10, NW Gaikwad3,10, DM Rotroff4,5, HR Kucera3, A Motsinger-Reif4,5, CP Smith4,5, LK Nieman6, DR Rubinow7, R Kaddurah-Daouk8,9 and PJ Schmidt1 Clinical evidence suggests that symptoms in premenstrual dysphoric disorder (PMDD) reflect abnormal responsivity to ovarian steroids. This differential steroid sensitivity could be underpinned by abnormal processing of the steroid signal. We used a pharmacometabolomics approach in women with prospectively confirmed PMDD (n = 15) and controls without menstrual cycle- related affective symptoms (n = 15). All were medication-free with normal menstrual cycle lengths. Notably, women with PMDD were required to show hormone sensitivity in an ovarian suppression protocol. Ovarian suppression was induced for 6 months with gonadotropin-releasing hormone (GnRH)-agonist (Lupron); after 3 months all were randomized to 4 weeks of estradiol (E2) or progesterone (P4). After a 2-week washout, a crossover was performed. Liquid chromatography/tandem mass spectrometry measured 49 steroid metabolites in serum. Values were excluded if 440% were below the limit of detectability (n = 21). Analyses were performed with Wilcoxon rank-sum tests using false-discovery rate (qo0.2) for multiple comparisons. PMDD and controls had similar basal levels of metabolites during Lupron and P4-derived neurosteroids during Lupron or E2/P4 conditions.
    [Show full text]
  • The Effects of Ovarian Hormones on Memory Bias and Progesterone Receptors in Female Rats
    The Effects of Ovarian Hormones on Memory Bias and Progesterone Receptors in Female Rats by Smita Patel A Thesis Submitted to the Department of Psychology Concordia University, Quebec In Partial Fulfillment of the Requirements for the Degree of Master of Arts (Psychology) August 2020 © Smita Patel, 2020 iii CONCORDIA UNIVERSITY School of Graduate Studies This is to certify that the thesis prepared By: Smita Patel Entitled: Effects of Ovarian Hormones on Memory Bias and Progesterone Receptors in Female Rats and submitted in partial fulfillment of the requirements for the degree of Master of Arts (Psychology) complies with the regulations of the University and meets the accepted standards with respect to originality and quality. Signed by the final examining committee: _____________________________________ Chair Andreas Arvanitogiannis _____________________________________ Examiner Andrew Chapman _____________________________________ Examiner Peter John Darlington _____________________________________ Thesis Supervisor Wayne Brake Approved by ____________________________________________________ Andreas Arvanitogiannis Pascale Sicotte Date ___________________________ iii ABSTRACT The Effects of Ovarian Hormones on Memory Bias and Progesterone Receptors in Female Rats Smita Patel, MA Concordia University, 2020 Ovarian hormones can bias female rats to use one memory system over another when navigating a novel or familiar environment, resulting in a memory bias. High levels of estrogen (E) promotes places memory while low level of E promotes response memory. However, little is known about the effects of progesterone (P) on memory bias. Experiment 1 determined whether P affects memory bias. Ovariectomized (OVX) female rats were trained in a plus- shaped maze, which assesses memory system bias, and received one of three hormonal treatments: Low 17β estradiol (E2), high E2 or high E2 + P.
    [Show full text]
  • Hormone Metabolites Reference Ranges | ZRT Laboratory
    Hormone Metabolites Reference Guide Hormone Metabolites Profiles Five profiles give a broad range of choices foran assessment of how patients are metabolizing a variety of hormones. They include: A wide array of estrogen, progesterone, and androgen metabolites useful for assessment of breast cancer risk Glucocorticoid metabolites, diurnal free cortisol, and diurnal free cortisone for adrenal assessment Diurnal 6-sulfatoxymelatonin (MT6s) to assess sleep / wake cycle dysfunction The xenoestrogen Bisphenol A (BPA) Sex steroid hormone metabolites results are useful for monitoring hormone therapy patients using patches, pellets or injectables. Adrenal Profile A picture of adrenal hormone metabolism. Consider for patients with adrenal dysfunction or stress. Useful as a second step of testing for those with adrenal fatigue symptoms, but whose saliva cortisol levels are normal (i.e., may indicate hyperexcretion of cortisol / excessive conversion to cortisone). Useful as a screening test for Addison’s or Cushing’s disease. Estrogen Essential Profile A baseline view of how a patient is metabolizing estrogens. Consider for anyone with a personal or family history of estrogen-dependent cancer (e.g., breast cancer). Estrogen Elite Profile Estrogen, progesterone, and select androgen metabolites with BPA. Consider for anyone with a personal or family history of estrogen-dependent cancer (e.g., breast cancer), patients with symptoms of estrogen/progesterone imbalance, men with prostate cancer risk, or patients who want to assess their exposure to BPA. Basic Profile A baseline view of sex steroid hormone metabolite levels plus total cortisol. Consider as a baseline assessment for hormone replacement therapy. Advanced Profile Our broadest view of sex steroid hormone metabolite levels and cortisol metabolism, with full diurnal melatonin and BPA.
    [Show full text]