DOCSLIB.ORG

A Dissertation Entitled Novel Actions of Steroid Receptors That Limit

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

A Dissertation Entitled Novel Actions of Steroid Receptors that Limit Treatment Response in Breast and Lung Cancers by Mugdha Patki Submitted to the Graduate Faculty as partial fulfillment of the requirements for the Doctor of Philosophy Degree in Biomedical Science Dr. Manohar Ratnam, Committee Chair Dr. Ivana de la Serna, Committee Member Dr. Stephan M. Patrick, Committee Member Dr. Edwin R. Sanchez, Committee Member Dr. Robert J. Trumbly, Committee Member Dr. Patricia R. Komuniecki, Dean College of Graduate Studies The University of Toledo December 2013 Copyright 2013, Mugdha Patki This document is copyrighted material. Under copyright law, no parts of this document may be reproduced without the expressed permission of the author. An Abstract of Novel Actions of Steroid Receptors that Limit Treatment Response in Breast and Lung Cancers by Mugdha Patki Submitted to the Graduate Faculty as partial fulfillment of the requirements for the Doctor of Philosophy Degree in Biomedical Science The University of Toledo December 2013 The primary physiological role of estrogens is the development of secondary sexual characteristics including development and function of the normal breast, reproductive system, bone homeostasis, cognitive functions and cardiovascular system. Estrogen has also been implicated as a major player in the progression of normal breast epithelial tissue to a carcinoma. The role of estrogens in breast cancer has been studied extensively and mainly attributed to the transcriptional activation of growth genes through the estrogen receptor. Along with activation of genes, estrogen is also responsible for repression of many genes. Anti-estrogens antagonize both gene activation and gene repression by estrogen. However, the significance and physiological relevance of gene repression by estrogen is poorly understood. mRNA profiling of MCF-7 breast cancer cells combined with a detailed gene ontology analysis revealed that the genes repressed by estrogen are mostly involved in tumor progression including invasion, drug resistance, angiogenesis and immune evasion. This study looks at the mechanism and impact of estrogen in repressing these tumor progression genes in breast cancer cells; we found that iii estrogen suppresses the invasiveness of breast cancer cells in a manner that is antagonized by anti-estrogens and is independent of HER2 status. These studies have implications in understanding the incidence of invasive breast cancer following hormone replacement therapy and long term anti-estrogen treatment and may also aid in the development of superior drugs for adjuvant treatment in breast cancer. Variability in response to chemotherapeutic drugs among patients is a longstanding issue in the treatment of several cancers. Likewise, in advanced lung cancer, patient response to the recently introduced drug, pemetrexed is variable. Pemetrexed is an antifolate approved for the first-line treatment of advanced non-squamous non-small cell lung cancer. Dexamethasone was added to the treatment regimen with pemetrexed to alleviate the serious side effect of severe skin rash observed in many patients. Dexamethasone is administered to patients the day before, the day of and the day after pemetrexed chemotherapy. We show that treatment of non-squamous non-small cell lung cancer cell line models with dexamethasone causes a reduction in the S-phase fraction of cells along with a decrease in the expression of thymidylate synthase and dihydrofolate reductase, which are primary and secondary targets of pemetrexed, respectively. As a consequence of these effects of dexamethasone pemetrexed cytotoxicity is attenuated. The response to dexamethasone is variable among different cell line models. Our correlative and functional studies demonstrate that the variability in pemetrexed sensitivity is causally related to variability in the expression of the glucocorticoid receptor isoform alpha, i.e. cells with relatively lower expression of the receptor fail to respond to dexamethasone iv and hence are sensitive to pemetrexed. These results could help to predict response to pemetrexed therapy leading to the development of individualized treatment strategies. v I lovingly dedicate my dissertation to my parents, Minal and Rajiv Patki, for always supporting my dreams and for their endless love and faith in my abilities. To my maternal grandfather, Ratnakar Mohile and to the memory of my maternal grandmother, Vimal Mohile, for being a source of inspiration and encouragement to me throughout my life. To my paternal grandmother, Asha Patki and to the memory of my paternal grandfather, Nilkanth Patki, for teaching me the importance of education and hard work. vi Acknowledgements I would like to thank my advisor Dr. Manohar Ratnam whose eternal wealth of knowledge and ideas have enlightened my life. I deeply acknowledge his guidance and patience in my research, his incessant spirit and love for science inspires me each day. I extend my sincere gratitude for his invaluable support and advice in my career goals and for his endless moral support which has made me a stronger person. I would like to thank Dr. Stephan Patrick for supporting me in every way and being my advisor during my time away from University of Toledo. I would like to thank Dr. Robert Trumbly for his advice and help with the analysis of the microarray results and bioinformatics. I would like to thank Dr. Edwin Sanchez for his invaluable suggestions; his experience in the field of nuclear receptors has helped me immensely in developing my research projects. I would also like to thank Dr. Ivana de la Serna for her support and advice. I am thankful to all the past and present members of the lab, Marcela d’Alincourt Salazar, Mesfin Gonit, Suneethi Sivakumaran, Venkatesh Chari, Lily Huang, Thomas McFall, Rayna Rosati and Shoya Yamada for their encouragement and camaraderie. A special thanks to Marcela d’Alincourt Salazar for teaching me everything in the lab and for her advice and friendship. I am thoroughly indebted to Lily Huang for helping me with my vii experiments in the last few months; my dissertation would not be complete without her assistance. I thank all the faculty and students of the Department of Biochemistry and Cancer Biology at University of Toledo for their support and a friendly work environment. I would especially like to acknowledge the efforts of Jenifer Zak in supporting me during my time away from Toledo. I would also like to thank the members of the labs on the eighth floor of Karmanos Cancer Institute for supporting me during my transition to Detroit. I am grateful to Dr. Cecilia Speyer for her advice in troubleshooting my experiments. I would like to extend my sincere gratitude to Dr. Larry Matherly for his support and involving me in the Wayne State University Cancer Biology program activities. I would also like to thank Amanda Cook and Jean Guerin for their assistance with everything. I feel blessed to have my wonderful family and bow to my parents’ for their efforts in encouraging and supporting me. I would like to express my gratitude to my cousin, Snehal Kharkar and to my boyfriend, Gopal Iyer for their love and moral support. Lastly, I would like to thank all of my friends for their constant encouragement and appreciation. A special thanks to my roommates Akshada Sawant and Gurpanna Saggu for making my time in Toledo memorable. I would like to thank Thomas McFall and Rayna Rosati for bringing joy to my life in Detroit. viii Table of Contents Abstract.............................................................................................................................. iii Acknowledgments.……………………………………………………………………... vii Table of contents...………………….……………………………….……………..……. ix List of tables………………………………………………………………………...…… xi List of figures…………………………………………………………………........…… xii 1 – Literature Review.............…………………………………………………………..... 1 1.1 Breast cancer epidemiology, etiology and biologic subtypes................................... 1 1.2 Estrogen biology....................................................................................................... 5 1.3 Adjuvant therapy in estrogen receptor positive breast cancer.................................. 8 1.4 Tamoxifen Endocrine therapy................................................................................ 13 1.5 Mechanisms of resistance to tamoxifen.................................................................. 16 1.6 Estrogen receptor structure and mechanism of action............................................ 19 1.7 Gene repression by estrogen and de-repression by tamoxifen............................... 25 1.8 Carcinoma of lung, epidemiology and etiology...................................................... 28 1.9 Classification and management of lung cancer...................................................... 29 1.10 Pemetrexed in the treatment of NSCLC – single agent and combination therapy.................................................................................................................. 33 1.11 Mechanism of action of pemetrexed..................................................................... 36 1.12 Mechanisms of resistance to pemetrexed............................................................. 38 ix 1.13 Therapeutic applications of glucocorticoids......................................................... 40 1.14 Mechanism of action of the glucocorticoid receptor............................................ 42 1.15 Mechanisms of resistance to glucocorticoids......................................................
Recommended publications
  • Tamoxifen As the First Targeted Long-Term Adjuvant Therapy for Breast

    Tamoxifen As the First Targeted Long-Term Adjuvant Therapy for Breast

    V C Jordan Adjuvant tamoxifen therapy for 21:3 R235–R246 Review breast cancer Tamoxifen as the first targeted long-term adjuvant therapy for breast cancer Correspondence V Craig Jordan should be addressed to V C Jordan Departments of Oncology and Pharmacology, Lombardi Comprehensive Cancer Center, Georgetown University Email Medical Center, Washington, District of Columbia 20057, USA [email protected] Abstract Tamoxifen is an unlikely pioneering medicine in medical oncology. Nevertheless, the medicine Key Words has continued to surprise us, perform, and save lives for the past 40 years. Unlike any other " breast medicine in oncology, it is used to treat all stages of breast cancer, ductal carcinoma in situ,and " endocrine therapy male breast cancer and pioneered the use of chemoprevention by reducing the incidence of breast cancer in women at high risk and induces ovulation in subfertile women! The impact of tamoxifen is ubiquitous. However, the power to save lives from this unlikely success story came from the first laboratory studies which defined that ‘longer was going to be better’ when tamoxifen was being considered as an adjuvant therapy. This is that success story, with a focus on the interdependent components of: excellence in drug discovery, investment in self-selecting young investigators, a conversation with Nature, a conversation between the laboratory and the clinic, and the creation of the Oxford Overview Analysis. Each of these Endocrine-Related Cancer factors was essential to propel the progress of tamoxifen to evolve as an essential part of the fabric of society. Endocrine-Related Cancer (2014) 21, R235–R246 Introduction ‘Science is adventure, discovery, new horizons, insight into our and invariably unsuccessful (except for childhood world, a means of predicting the future and enormous power leukemia).
  • Folliculo-Stellate Cells: Paracrine Communicators in the Anterior Pituitary John Morris* and Helen Christian*

    Folliculo-Stellate Cells: Paracrine Communicators in the Anterior Pituitary John Morris* and Helen Christian*

    The Open Neuroendocrinology Journal, 2011, 4, 77-89 77 Open Access Folliculo-stellate Cells: Paracrine Communicators in the Anterior Pituitary John Morris* and Helen Christian* Department of Physiology, Anatomy & Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK Abstract: Most research on the anterior pituitary (adenohypophysis) has concentrated on the endocrine cells characterized by their complement of cytoplasmic dense-cored vesicles containing the classic anterior pituitary hormones. However it has become increasingly clear over the last 20 years that cells first identified more than 50 years ago in the basis that they lack such dense-cored vesicles and now known generically as folliculo-stellate or follicular cells have important physiological functions and act as an adenohypophysis wide communication system. This brief review reveals the need for this communication system, what we know of the plethora of products secreted by Folliculo-Stellate cells, the many receptors to which they respond, and in particular, the role of these enigmatic cells in the physiology of the stress/immune axis, the gonadotroph cells and the pituitary vasculature. Finally we review the current evidence that cells in this category can act as stem cells in the adult pituitary. Keywords: Annexin 1, ABC-transporter, folliculo-stellate. THE NEED FOR COMMUNICATION IN THE basis of morphological criteria [4]. They were named for ANTERIOR PITUITARY their extensive star-like radiating processes and for the microvillus-lined follicles which are formed where the F-S The need for local communication in the nervous system has always been accepted, but has often been overlooked in cells come together.
  • (12) United States Patent (10) Patent No.: US 8,623.422 B2 Hansen Et Al

    (12) United States Patent (10) Patent No.: US 8,623.422 B2 Hansen Et Al

    USOO8623422B2 (12) United States Patent (10) Patent No.: US 8,623.422 B2 Hansen et al. (45) Date of Patent: *Jan. 7, 2014 (54) COMBINATION TREATMENT WITH 5,668,161 A 9/1997 Talley et al. STRONTUM FOR THE PROPHYLAXIS 5,681,842 A 10, 1997 Dellaria et al. AND/OR TREATMENT OF CARTILAGE 5,686.460 A 11/1997 Nicolai et al. AND/OR BONE CONDITIONS 5,686,470 A 11/1997 Weier et al. 5,696,431 A 12/1997 Giannopoulos et al. 5,707,980 A 1/1998 Knutson (75) Inventors: Christian Hansen, Vedback (DK); 5,719,163 A 2f1998 Norman et al. Henrik Nilsson, Copenhagen (DK); 5,750,558 A 5/1998 Brooks et al. Stephan Christgau, Gentofte (DK) 5,753,688 A 5/1998 Talley et al. 5,756,530 A 5/1998 Lee et al. (73) Assignee: Osteologix A/S, Copenhagen (DK) 5,756,531 A 5/1998 Brooks et al. 5,760,068 A 6/1998 Talley et al. (*) Notice: Subject to any disclaimer, the term of this 5,776,967 A 7/1998 Kreft et al. patent is extended or adjusted under 35 5,776,984. A 7/1998 Dellaria et al. U.S.C. 154(b) by 558 days. 5,783,597 A 7/1998 Beers et al. This patent is Subject to a terminal dis 5,807,873 A 9, 1998 Nicolai et al. claimer. 5,824,699 A 10, 1998 Kreft et al. 5,830,911 A 11/1998 Failli et al. 5,840,924 A 11/1998 Desmond et al.
  • Folliculostellate Cell Network: a Route for Long- Distance Communication in the Anterior Pituitary

    Folliculostellate Cell Network: a Route for Long- Distance Communication in the Anterior Pituitary

    Folliculostellate cell network: A route for long- distance communication in the anterior pituitary Teddy Fauquier*, Nathalie C. Gue´ rineau*, R. Anne McKinney†, Karl Bauer‡, and Patrice Mollard*§ *Institut National de la Sante´et de la Recherche Me´dicale (INSERM) Unite´469, Centre National de la Recherche Scientifique–INSERM de Pharmacologie–Endocrinologie, 141 Rue de la Cardonille, 34094 Montpellier Cedex 5, France; †Brain Research Institute, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland; and ‡Max-Planck-Institut fu¨r Experimentelle Endokrinologie, Feodor-Lynen-Strasse 7, 30625 Hannover, Germany Edited by Michael V. L. Bennett, Albert Einstein College of Medicine, Bronx, NY, and approved May 9, 2001 (received for review July 21, 2000) All higher life forms critically depend on hormones being rhyth- transfer within the gland. FS cells display a star-shaped cyto- mically released by the anterior pituitary. The proper functioning plasmic configuration intermingled between hormone-secreting of this master gland is dynamically controlled by a complex set of cells. The organization of FS cells within the parenchyma forms regulatory mechanisms that ultimately determine the fine tuning a three-dimensional anatomical network, in the meshes of which of the excitable endocrine cells, all of them heterogeneously the endocrine cells reside (15, 16). Very little is known about the distributed throughout the gland. Here, we provide evidence for functioning of this FS cell network, in particular with regard to an intrapituitary communication system by which information is the dynamics of cellular͞intercellular messages. To study the transferred via the network of nonendocrine folliculostellate (FS) behavior of this network, we measured multicellular changes in 2ϩ cells.
  • Estrogen Stimulation of P450 Cholesterol Side-Chain Cleavage Activity in Cultures of Human Placental Syncytiotrophoblasts'

    Estrogen Stimulation of P450 Cholesterol Side-Chain Cleavage Activity in Cultures of Human Placental Syncytiotrophoblasts'

    BIOLOGY OF REPRODUCTION 56, 272-278 (1997) Estrogen Stimulation of P450 Cholesterol Side-Chain Cleavage Activity in Cultures of Human Placental Syncytiotrophoblasts' Jeffery S. Babischkin,3 Randall W. Grimes,3 Gerald J. Pepe, 4 and Eugene D. Albrecht2,3 Departments of Obstetrics/Gynecology/Reproductive Sciences and Physiology,' Center for Studies in Reproduction, University of Maryland School of Medicine, Baltimore, Maryland 21201 Department of Physiology Eastern Virginia Medical School, Norfolk, Virginia 23501 ABSTRACT biochemical differentiation of the latter cells that is mani- fested as an increase in expression of the LDL receptor and Downloaded from https://academic.oup.com/biolreprod/article/56/1/272/2760805 by guest on 29 September 2021 The present study determined whether estrogen has a role in regulating the P450 cholesterol side-chain cleavage enzyme P450,,, enzyme system. (P450_cc) and/or de novo/deesterification cholesterol pathways Recently, we reported that LDL uptake was increased in involved in progesterone biosynthesis within human syncytiotro- human syncytiotrophoblast cells cultured with estrogen [7] phoblasts. Human placental syncytiotrophoblasts were cultured and suggested that estrogen also regulates key steps in the for 48 h with estradiol, and P450,,,cc activity was determined by placental progesterone pathway in human pregnancy. How- the formation of progesterone from 25-hydroxycholesterol. Es- ever, it remains to be determined whether estrogen also reg- tradiol at 10 7 or 10 6 M and 25-hydroxycholesterol increased
  • Involvement of the Gp130 Cytokine Transducer in Mtt/S Pituitary

    Involvement of the Gp130 Cytokine Transducer in Mtt/S Pituitary

    European Journal of Endocrinology (2004) 151 595–604 ISSN 0804-4643 EXPERIMENTAL STUDY Involvement of the gp130 cytokine transducer in MtT/S pituitary somatotroph tumour development in an autocrine-paracrine model Mariana Graciarena, Alberto Carbia-Nagashima, Chiara Onofri1, Carolina Perez-Castro, Damiana Giacomini, Ulrich Renner1,Gu¨nter K Stalla1 and Eduardo Arzt Laboratorio de Fisiologı´a y Biologı´a Molecular, Departamento de Fisiologı´a y Biologı´a Molecular y Celular, FCEN, Universidad de Buenos Aires, C1428EHA Buenos Aires, Argentina and 1Department of Endocrinology, Max Planck Institute of Psychiatry, 80804 Munich, Germany (Correspondence should be addressed to E Arzt; Email: [email protected]) (M Graciarena and A Carbia-Nagashima contributed equally to this paper) Abstract Objective: gp130 cytokines are placed as auto-paracrine regulators of pituitary function, since they, as well as their receptors, have been shown to be expressed in and to act in normal and tumoral anterior pituitary cells. The objective of this work was to study their involvement in a model that shows the interaction between different cellular types that participate in a tumorigenic process. Design: The dependence of a pituitary somatotrophic cell line (MtT/S) on a gp130 cytokine-producing folliculostellate (FS) cell line (TtT/GF) for tumorigenesis in vivo has been described. In order to study the participation of gp130 cytokines in the auto-paracrine stimulation of MtT/S growth, we gener- ated MtT/S gp130 sense (gp130-S) and gp130 antisense (gp130-AS) clones stably transfected with pcDNA3/gp130 sense and pcDNA3/gp130 antisense vectors respectively. Methods and results: Functional characterization studies revealed that gp130-AS clones have an inhib- ited gp130 signalling, and proliferation studies showed that they have an impaired response to gp130 cytokines but respond normally to other independent stimuli.
  • Characterization of Immune Response in Corticosteroid-Refractory Severe Asthma in Humans and Mice

    Characterization of Immune Response in Corticosteroid-Refractory Severe Asthma in Humans and Mice

    Characterization of Immune Response in Corticosteroid-refractory Severe Asthma in Humans and Mice by Mahesh Raundhal Masters of Science (Biotechnology), V. G. Vaze College, 2008 Bachelors of Science (Biotechnology), Kishinchand Chellaram College, 2006 Submitted to the Graduate Faculty of School of Medicine in partial fulfillment of the requirements for the degree of Doctor of Philosophy University of Pittsburgh 2015 UNIVERSITY OF PITTSBURGH School of Medicine This thesis was presented by Mahesh Raundhal It was defended on August 24th, 2015 and approved by Dissertation Advisor and Chairperson: Prabir Ray, PhD Professor, Departments of Medicine and Immunology Anuradha Ray, PhD Professor, Departments of Medicine and Immunology Sally Wenzel, MD Professor, Department of Medicine Jay Kolls, MD Professor, Departments of Pediatrics and Immunology Saumendra Sarkar, PhD Associate Professor, Department of Microbiology & Molecular Genetics and Immunology ii Characterization of Immune Response in Corticosteroid-refractory Severe Asthma in Humans and Mice Mahesh Raundhal, M.Sc. University of Pittsburgh, 2015 Copyright © by Mahesh Raundhal 2015 iii Abstract Severe asthma (SA) remains a poorly controlled disease despite use of high doses of systemic corticosteroids (CS) although mild-moderate asthma (MMA) is responsive to low dose inhaled CS. This suggests that SA cannot be solely orchestrated by Th2 cells, which are dominant in milder disease. Analysis of broncholalveolar lavage cells isolated from MMA and SA patients revealed a significantly greater IFN- (Th1) immune response in the airways of severe asthmatics with lower Th2 and IL-17 responses. We modeled this complex immune response seen in human SA in mice including poor response to CS. Ifng-/- mice subjected to this SA model failed to mount airway hyperresponsiveness (AHR) without appreciable effect on airway inflammation.
  • Tamoxifen As the First Targeted Long-Term Adjuvant Therapy For

    Tamoxifen As the First Targeted Long-Term Adjuvant Therapy For

    V C Jordan Adjuvant tamoxifen therapy for 21:3 R235–R246 Review breast cancer Tamoxifen as the first targeted long-term adjuvant therapy for breast cancer Correspondence V Craig Jordan should be addressed to V C Jordan Departments of Oncology and Pharmacology, Lombardi Comprehensive Cancer Center, Georgetown University Email Medical Center, Washington, District of Columbia 20057, USA [email protected] Abstract Tamoxifen is an unlikely pioneering medicine in medical oncology. Nevertheless, the medicine Key Words has continued to surprise us, perform, and save lives for the past 40 years. Unlike any other " breast medicine in oncology, it is used to treat all stages of breast cancer, ductal carcinoma in situ,and " endocrine therapy male breast cancer and pioneered the use of chemoprevention by reducing the incidence of breast cancer in women at high risk and induces ovulation in subfertile women! The impact of tamoxifen is ubiquitous. However, the power to save lives from this unlikely success story came from the first laboratory studies which defined that ‘longer was going to be better’ when tamoxifen was being considered as an adjuvant therapy. This is that success story, with a focus on the interdependent components of: excellence in drug discovery, investment in self-selecting young investigators, a conversation with Nature, a conversation between the laboratory and the clinic, and the creation of the Oxford Overview Analysis. Each of these Endocrine-Related Cancer factors was essential to propel the progress of tamoxifen to evolve as an essential part of the fabric of society. Endocrine-Related Cancer (2014) 21, R235–R246 Introduction ‘Science is adventure, discovery, new horizons, insight into our and invariably unsuccessful (except for childhood world, a means of predicting the future and enormous power leukemia).
  • Existence of Long-Lasting Experience-Dependent Plasticity in Endocrine Cell Networks

    Existence of Long-Lasting Experience-Dependent Plasticity in Endocrine Cell Networks

    ARTICLE Received 3 May 2011 | Accepted 24 Nov 2011 | Published 3 Jan 2012 DOI: 10.1038/ncomms1612 Existence of long-lasting experience-dependent plasticity in endocrine cell networks David J. Hodson1 , 2 , 3 , Marie Schaeffer 1 , 2 , 3 , 4 , N i c o l a R o m a n ò 1 , 2 , 3 , Pierre Fontanaud 1 , 2 , 3 , Chrystel Lafont1 , 2 , 3 , Jerome Birkenstock1 , 2 , 3 , Fran ç ois Molino1 , 2 , 3 , Helen Christian5 , J o e L o c k e y 5 , Danielle Carmignac 6 , Marta Fernandez-Fuente6 , Paul Le Tissier6 & Patrice Mollard1 , 2 , 3 Experience-dependent plasticity of cell and tissue function is critical for survival by allowing organisms to dynamically adjust physiological processes in response to changing or harsh environmental conditions. Despite the conferred evolutionary advantage, it remains unknown whether emergent experience-dependent properties are present in cell populations organized as networks within endocrine tissues involved in regulating body-wide homeostasis. Here we show, using lactation to repeatedly activate a specifi c endocrine cell network in situ in the mammalian pituitary, that templates of prior demand are permanently stored through stimulus- evoked alterations to the extent and strength of cell – cell connectivity. Strikingly, following repeat stimulation, evolved population behaviour leads to improved tissue output. As such, long-lasting experience-dependent plasticity is an important feature of endocrine cell networks and underlies functional adaptation of hormone release. 1 CNRS, UMR-5203, Institut de G é nomique Fonctionnelle , Montpellier F-34000, France . 2 INSERM , U661, Montpellier F-34000, France . 3 UMR-5203, Universit é s de Montpellier 1 & 2 , Montpellier F-34000, France .
  • The Folliculostellate Cells in the Pituitary Gland

    The Folliculostellate Cells in the Pituitary Gland

    Editorial THE FOLLICULOSTELLATE CELLS IN THE PITUITARY GLAND D. C. Danila Massachusetts General Hospital and Harvard Medical School, Boston The pituitary cells are regulated by numerous endocrine, paracrine and autocrine feed-back pathways, and their hormone secretion exerts major control over the function of several endocrine glands as well as a wide range of physiologic states. In the anterior pituitary, secretory cells are in close interconnection with folliculostellate cells, agranular functional units of an interactive endocrine networking. First described in 1953 by Rinehart et al. (1), accounting for 5-10% of cells in the anterior pituitary, the role of the folliculostellate cells in the pituitary has been increasingly recognized and further characterized by recent studies. It has been suggested that the folliculostellate cells, derived from neuroectoderm, form a three dimensional network, supporting and modulating endocrine cells by intercellular communication in a paracrine manner (2, 3). In the pituitary, it has been shown that a subset of pituitary adenomas has significant numbers of folliculostellate cells (4, 5) and, furthermore, pituitary tumors consisting only of folliculostellate cells have been described (4). Folliculostellate cells also produce a number of bioactive peptides including basic fibroblast growth factor (6), vascular epithelial growth factor (7), IL-6 (8), and neuronal nitric oxide synthesis (9). It has been demonstrated that folliculostellate cells also produce lipocortin-1 (10), a key inhibitory mediator of glucocorticoids on corticotrophin secretion, at both the hypothalamic and pituitary levels (11). The regulatory interactions between folliculostellate and lactotroph cells (12, 13) and the role of folliculostellate cells in immune system modulation (14, 15) have also been reported.
  • Uva-DARE (Digital Academic Repository)

    Uva-DARE (Digital Academic Repository)

    UvA-DARE (Digital Academic Repository) The TSH receptor in the pituitary and its clinical relevance Brokken, L.J.S. Publication date 2002 Link to publication Citation for published version (APA): Brokken, L. J. S. (2002). The TSH receptor in the pituitary and its clinical relevance. General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam (https://dare.uva.nl) Download date:04 Oct 2021 7 7 Generall Discussion G€N€MiG€N€Mi DISCUSSION 7.11 INTRODUCTION Inn many patients with Graves' hyperthyroidism, plasma thyrotropin (TSH) values remain low despitee adequate antithyroid treatment, as witnessed by a return of T4 and T3 serum values to normal,, and by clinical euthyroidism. This has been attributed to a so-called 'delayed recoveryy of the pituitary-thyroid axis'.
  • S Health and Menopause

    S Health and Menopause

    National Heart, Lung, and Blood Institute Office of Research on Women’s Health Giovanni Lorenzini Medical Science Foundation I NTERNATIONAL P OSITION P APER on W OMEN’ S H EALTH AND M ENOPAUSE: ACOMPREHENSIVE A PPROACH NATIONAL INSTITUTES OF HEALTH I NTERNATIONAL P OSITION P APER on W OMEN’ S H EALTH AND M ENOPAUSE: ACOMPREHENSIVE A PPROACH NATIONAL HEART, LUNG, AND BLOOD INSTITUTE OFFICE OF RESEARCH ON WOMEN’S HEALTH NATIONAL INSTITUTES OF HEALTH AND GIOVANNI LORENZINI MEDICAL SCIENCE FOUNDATION NIH PUBLICATION NO. 02-3284 JULY 2002 CHAIRS AND EDITORS Chair and Editor Cochair and Coeditor Nanette K. Wenger, M.D. Claude J. M. Lenfant, M.D. Professor of Medicine (Cardiology) Director Emory University School of Medicine National Heart, Lung, and Blood Institute Atlanta, GA, U.S.A. National Institutes of Health Bethesda, MD, U.S.A. Cochair and Coeditor Rodolfo Paoletti, M.D. Cochair and Coeditor Professor of Pharmacology Vivian W. Pinn, M.D. Director, Department of Pharmacological Sciences Associate Director for Research on University of Milan Women’s Health Milan, Italy Director, Office of Research on Women’s Health National Institutes of Health Bethesda, MD, U.S.A. PANEL MEMBERS Elizabeth Barrett-Connor, M.D. Louise A. Brinton, Ph.D. Professor and Chief Chief, Environmental Epidemiology Branch Division of Epidemiology National Cancer Institute Department of Family and Preventive Medicine National Institutes of Health University of California, San Diego School of Bethesda, MD, U.S.A. Medicine La Jolla, CA, U.S.A. Aila Collins, Ph.D. Associate Professor Martin H. Birkhäuser, M.D. Psychology Section Professor Department of Clinical Neuroscience Division of Gynecological Endocrinology Karolinska Institute Department of Obstetrics and Gynecology Stockholm, Sweden University of Bern Bern, Switzerland II Peter Collins, M.D.