Molecular Biology of the Parathyroid

212 Pages·2005·4.886 MB·English

by  Tally Naveh-Many

MOLECULAR BIOLOGY INTELLIGENCE UNIT
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OLECULAR IOLOGY
I
NTELLIGENCE
U
NIT
Molecular Biology
of the Parathyroid
Tally Naveh-Many, Ph.D.
Minerva Center for Calcium and Bone Metabolism
Nephrology Services
Hadassah Hebrew University Medical Center
Jerusalem, Israel
LANDES BIOSCIENCE / EUREKAH.COM KLUWER ACADEMIC / PLENUM PUBLISHERS
GEORGETOWN, TEXAS NEW YORK, NEW YORK
U.S.A. U.S.A.
M B P
OLECULAR IOLOGY OF THE ARATHYROID
Molecular Biology Intelligence Unit
Landes Bioscience / Eurekah.com
Kluwer Academic / Plenum Publishers
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Molecular Biology of the Parathyroid, edited by Tally Naveh-Many, Landes / Kluwer dual imprint / Landes
series: Molecular Biology Intelligence Unit
ISBN: 0-306-47847-1
While the authors, editors and publisher believe that drug selection and dosage and the specifications and
usage of equipment and devices, as set forth in this book, are in accord with current recommendations and
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Library of Congress Cataloging-in-Publication Data
Molecular biology of the parathyroid / [edited by] Tally Naveh-Many.
p. ; cm. -- (Molecular biology intelligence unit)
Includes bibliographical references and index.
ISBN 0-306-47847-1
1. Parathyroid glands--Molecular aspects. 2. Parathyroid hormone. I. Naveh-Many, Tally. II. Series:
Molecular biology intelligence unit (Unnumbered)
[DNLM: 1. Parathyroid Glands--physiology. 2. Molecular Biology. 3. Parathyroid Glands--physiopathol-
ogy. 4. Parathyroid Hormone--physiology. WK 300 M718 2005]
QP188.P3M654 2005
612.4'4--dc22
2004023419
To Dani, Assaf, Yoav and Amir
CONTENTS
Preface ................................................................................................xiii
1. Development of Parathyroid Glands......................................................1
Thomas Günther and Gerard Karsenty
Physiology of the Parathyroid Glands....................................................1
Development of Parathyroid Glands in Vertebrates...............................1
Genetic Control of Parathyroid Gland Development............................3
2. Parathyroid Hormone, from Gene to Protein ........................................8
Osnat Bell, Justin Silver and Tally Naveh-Many
The Prepro PTH Peptide......................................................................8
Homology of the Mature PTH .............................................................9
The PTH mRNA................................................................................10
Cloning of the PTH cDNAs ...............................................................11
Homology of the cDNA Sequences.....................................................12
Structure of the PTH mRNA..............................................................18
The PTH Gene...................................................................................21
The 5’ Flanking Region.......................................................................24
The 3' Flanking Region.......................................................................24
Chromosomal Location of the Human PTH Gene .............................25
3. Toward an Understanding of Human Parathyroid
Hormone Structure and Function........................................................29
Lei Jin, Armen H. Tashjian, Jr., and Faming Zhang
PTH and Its Receptor Family .............................................................29
PTH Structural Determination...........................................................30
Structural Based Design of PTH Analogs............................................37
4. The Calcium Sensing Receptor............................................................44
Shozo Yano and Edward M. Brown
Biochemical Characteristics of the CaR...............................................45
Disorders Presenting with Abnormalities in Calcium
Metabolism and in the CaR ............................................................47
Signaling Pathways of the CaR............................................................49
Drugs Acting on the CaR....................................................................50
5. Regulation of Parathyroid Hormone mRNA Stability
by Calcium and Phosphate...................................................................57
Rachel Kilav, Justin Silver and Tally Naveh-Many
Regulation of the Parathyroid Gland by Calcium
and Phosphate.................................................................................57
Protein Binding and PTH mRNA Stability.........................................58
Identification of the PTH mRNA 3’-UTR Binding
Proteins and Their Function ...........................................................61
Identification of the Minimal cis Acting Protein Binding
Element in the PTH mRNA 3’-UTR..............................................62
The Structure of the PTH cis Acting Element .....................................64
6. In Silico Analysis of Regulatory Sequences in the Human
Parathyroid Hormone Gene.................................................................68
Alexander Kel, Maurice Scheer and Hubert Mayer
Global Homology of PTH Gene between Human
and Mouse ......................................................................................71
Computer Assisted Search for Potential Cis-Regulatory
Elements in PTH Gene...................................................................75
Phylogenetic Footprint: Identification of TF Binding Sites
by Comparison of Regulatory Regions of PTH Gene
of Different Organisms....................................................................78
Discussion...........................................................................................80
7. Regulation of Parathyroid Hormone Gene Expression
by 1,25-Dihydroxyvitamin D...............................................................84
Tally Naveh-Many and Justin Silver
Transcriptional Regulation of the PTH Gene
by 1,25(OH)D ..............................................................................84
2 3
Calreticulin and the Action of 1,25(OH)D
2 3
on the PTH Gene ...........................................................................89
PTH Degradation...............................................................................90
Secondary Hyperparathyroidism and Parathyroid
Cell Proliferation.............................................................................90
8. Vitamin D Analogs for the Treatment of Secondary
Hyperparathyroism in Chronic Renal Failure.......................................95
Alex J. Brown
Pathogenesis of Secondary Hyperparathyroidism in Chronic
Renal Failure...................................................................................95
Treatment of Secondary Hyperparathyroidism....................................96
Mechanisms for the Selectivity of Vitamin D Analogs.......................104
Future Perspectives............................................................................109
9. Parathyroid Gland Hyperplasia in Renal Failure................................113
Adriana S. Dusso, Mario Cozzolino and Eduardo Slatopolsky
Parathyroid Tissue Growth in Normal Conditions
and in Renal Failure......................................................................114
Dietary Phosphate Regulation of Parathyroid Cell Growth
in Uremia......................................................................................116
Vitamin D Regulation of Uremia- and High Phosphate-Induced
Parathyroid Cell Growth...............................................................120
Calcium Regulation of Uremia-Induced Parathyroid Growth ...........123
10. Molecular Mechanisms in Parathyroid Tumorigenesis.......................128
Eitan Friedman
Oncogenes Involved in Parathyroid Tumor Development.................129
Tumor Suppressor Genes Involved in Parathyroid
Tumorigenesis...............................................................................130
Other Molecular Pathways Involved in Parathyroid
Tumorigenesis...............................................................................132
11. Molecular Genetic Abnormalities in Sporadic
Hyperparathyroidism.........................................................................140
Trisha M. Shattuck, Sanjay M. Mallya and Andrew Arnold
Implications of the Monoclonality of Parathyroid Tumors................141
Molecular Genetics of Parathyroid Adenomas...................................142
Molecular Genetics of Parathyroid Carcinoma..................................151
Molecular Genetics of Secondary and Tertiary
Hyperparathyroidism ....................................................................152
12. Genetic Causes of Hypoparathyroidism.............................................159
Rachel I. Gafni and Michael A. Levine
Disorders of Parathyroid Gland Formation .......................................159
Disorders of Parathyroid Hormone Synthesis or Secretion ................167
Parathyroid Gland Destruction .........................................................170
Resistance to Parathyroid Hormone..................................................171
13. Skeletal and Reproductive Abnormalities in Pth-Null Mice ...............179
Dengshun Miao, Bin He, Beate Lanske, Xiu-Ying Bai,
Xin-Kang Tong, Geoffrey N. Hendy, David Goltzman
and Andrew C. Karaplis
Results...............................................................................................180
Discussion.........................................................................................188
Materials and Methods......................................................................193
Index..................................................................................................197
EDITOR
Tally Naveh-Many
Minerva Center for Calcium and Bone Metabolism
Nephrology Services
Hadassah Hebrew University Medical Center
Jerusalem, Israel
Chapters 2, 5, 7
CONTRIBUTORS
Andrew Arnold Mario Cozzolino
Center for Molecular Medicine Renal Division
University of Connecticut Health Center Washington University School
Farmington, Connecticut, U.S.A. of Medicine
Chapter 11 St. Louis, Missouri, U.S.A.
Chapter 9
Xiu-Ying Bai
Division of Endocrinology Adriana S. Dusso
Department of Medicine and Lady Davis Renal Division
Institute for Medical Research Washington University School
Sir Mortimer B. Davis-Jewish General of Medicine
Hospital St. Louis, Missouri, U.S.A.
McGill University Chapter 9
Montreal, Canada
Chapter 13 Eitan Friedman
Institute of Genetics
Osnat Bell Sheba Medical Center
Minerva Center for Calcium Tel Hashomer, Israel
and Bone Metabolism Chapter 10
Nephrology Services
Hadassah Hebrew University Rachel I. Gafni
Medical Center Division of Pediatric Endocrinology
Jerusalem, Israel University of Maryland Medical Systems
Chapter 2 Baltimore, Maryland, U.S.A.
Chapter 12
Alex J. Brown
Renal Division David Goltzman
Washington University School Calcium Research Laboratory
of Medicine and Department of Medicine
St. Louis, Missouri, U.S.A. McGill University Health Centre
Chapter 8 and Royal Victoria Hospital
McGill University
Edward M. Brown Montreal, Canada
Endocrine-Hypertension Unit Chapter 13
Brigham and Women’s Hospital
Boston, Massachusetts, U.S.A.
Chapter 4
Thomas Günther Alexander Kel
Department of Obstetrics Department of Research
and Gynecology and Development
Freiburg University Medical Center BIOBASE GmbH
Freiburg, Germany Wolfenbüttel, Germany
Chapter 1 Chapter 6
Bin He Rachel Kilav
Division of Endocrinology Minerva Center for Calcium
Department of Medicine and Lady Davis and Bone Metabolism
Institute for Medical Research Nephrology Services
Sir Mortimer B. Davis-Jewish General Hadassah Hebrew University
Hospital Medical Center
McGill University Jerusalem, Israel
Montreal, Canada Chapter 5
Chapter 13
Beate Lanske
Geoffrey N. Hendy Department of Oral and Developmental
Calcium Research Laboratory Biology
and Department of Medicine Forsyth Institute and Harvard School
McGill University Health Centre of Dental Medicine
and Royal Victoria Hospital Boston, Massachusetts, U.S.A.
McGill University Chapter 13
Montreal, Canada
Chapter 13 Michael A. Levine
Department of Pediatric Endocrinology
Lei Jin The Children's Hospital
Suntory Pharmaceutical Research at The Cleveland Clinic
Laboratories LLC Cleveland Clinic Lerner College
Cambridge, Massachusetts, U.S.A. of Medicine of Case Western
Chapter 3 Reserve University
Cleveland, Ohio, U.S.A.
Andrew C. Karaplis Chapter 12
Division of Endocrinology
Department of Medicine and Lady Davis Dengshun Miao
Institute for Medical Research Calcium Research Laboratory
Sir Mortimer B. Davis-Jewish General and Department of Medicine
Hospital McGill University Health Centre
McGill University and Royal Victoria Hospital
Montreal, Canada McGill University
Chapter 13 Montreal, Canada
Chapter 13
Gerard Karsenty
Department of Molecular
and Human Genetics
Baylor College of Medicine
Houston, Texas, U.S.A.
Chapter 1
Sanjay M. Mallya Armen H. Tashjian, Jr.
Center for Molecular Medicine Department of Cancer Cell Biology
University of Connecticut School Harvard School of Public Health
of Medicine and Department of Biological
Farmington, Connecticut, U.S.A. Chemistry and Molecular
Chapter 11 Pharmacology
Harvard Medical School
Hubert Mayer Boston, Massachusetts, U.S.A.
Department of Gene Regulation Chapter 3
Gesellschaft für Biotechnologische
Forschung Xin-Kang Tong
Braunschweig, Germany Division of Endocrinology
Chapter 6 Department of Medicine and Lady Davis
Institute for Medical Research
Maurice Scheer Sir Mortimer B. Davis-Jewish General
Department of Research Hospital
and Development McGill University
BIOBASE GmbH Montreal, Canada
Wolfenbüttel, Germany Chapter 13
Chapter 6
Shozo Yano
Trisha M. Shattuck Department of Nephrology
Center for Molecular Medicine Ichinomiya Municipal Hospital
University of Connecticut School Ichinomiya, Aichi, Japan
of Medicine Chapter 4
Farmington, Connecticut, U.S.A.
Chapter 11 Faming Zhang
Lilly Research Laboratories
Justin Silver Eli Lilly & Company
Minerva Center for Calcium Indianapolis, Indiana, U.S.A.
and Bone Metabolism Chapter 3
Nephrology Services
Hadassah Hebrew University
Medical Center
Jerusalem, Israel
Chapters 2, 5, 7
Eduardo Slatopolsky
Renal Division
Washington University School
of Medicine
St. Louis, Missouri, U.S.A.
Chapter 9