Gene Engineering in Endocrinology / Edition 1

by Margaret A. Shupnik

Overview

During the past five to ten years, a variety of tools has been developed in the disciplines of both gene engineering, and molecular and structural biology. Some of these advances have permitted scientists not only to identify and characterize genes, but also to target these genes by disruption, thus eliminating their function in living animals, and to det- mine the biological responses to altered gene products. This has particular significance in endocrine systems, in which feedback mechanisms between the hypothalamus, pi- itary, and end organs are critical in normal physiology. Interpretation of the physiological significance, or the site of action of specific molecules in this context, has been difficult prior to transgenic technology. Major advances have occurred specifically in the areas of growth and development, and of reproduction. Coupled with analysis of naturally occurring mutations in humans, the use of transgenic animals and in vitro systems has recently allowed endocrinologists to understand the importance of specific thyroid hormone receptor isoforms in vivo, the molecular basis for generalized resistance to thyroid hormones via mutations in the nuclear receptor, and mechanisms for suppressing gene transcription. Previously designated “orphan rec- tors,” such as steroidogenic factor-1, were demonstrated to have critical roles in dev- opment and reproduction. Other nuclear receptors—including those for thyroid hormone, estrogens, androgens, and progesterone—were shown to bind to coactivator and co- pressor proteins that modified their transcriptional activity, and contributed to the ce- specific effects of the hormones.

Product Details

ISBN-13:	9781617371479
Publisher:	Springer-Verlag New York, LLC
Publication date:	11/09/2010
Series:	Contemporary Endocrinology , #22
Edition description:	Softcover reprint of hardcover 1st ed. 2000
Pages:	428
Product dimensions:	7.01(w) x 10.00(h) x 0.04(d)

About the Author

Shupnik, Margaret A., PhD (Univ of Virginia Health Sciences Center)

Table of Contents

I Growth, Development, and Metabolism.- 1 Differential Cell Signaling and Gene Activation by the Human Growth Hormone Receptor: From Cell Surface to Cell Nucleus.- 2 Insulin Action: Molecular Mechanisms and Determinants of Specificity.- 3 Ets Transcription Factors: Nuclear Integrators of Signaling Pathways Regulating Endocrine Gene Expression and Carcinogenesis.- 4 Pit-1 Expression, Regulation, and Modulation of Multiple Pituitary Genes.- 5 Subnuclear Trafficking of Glucocorticoid Receptors: General Mechanisms and Specific Recruitment to a Unique Target Site by Tethering to a DNA-Bound POU Domain Protein.- 6 Thyroid Hormone Receptors and Their Multiple Transcriptional Roles.- 7 Models of Resistance to Thyroid Hormone.- 8 Thyroid Hormone Receptor Family Members: Homodimers, Heterodimers, and Mechanisms of Transcriptional Repression.- 9 SF-1 and DAX-1: A Dynamic Duo in Endocrine Development.- II Reproductive System.- 10 Gene Knockout Models to Study the Hypothalamus-Pituitary-Gonadal Axis.- 11 Transgenic Approaches to Study Developmental Expression and Regulation of the Gonadotropin Genes.- 12 Molecular Events Defining Follicular Developments and Steroidogenesis in the Ovary.- 13 Regulation of Inhibin Subunit Gene Expression by Gonadotropins and cAMP in Ovarian Granulosa Cells.- 14 Placental Trophoblast Cells: Transcriptional Regulation and Differentiation.- 15 Alternative Splicing of mRNAs for cAMP-Responsive Transcriptional Factors and Modulation of Gene Transcription in the Testis.- 16 The Androgen Receptor, Androgen Insensitivity, and Prostate Cancer.- 17 Genetic Determination of Androgen Responsiveness.- 18 Steroid Receptor Regulation by Phosphorylation and Cell Signaling Pathways.- 19 Steroid Receptor Actions: Agonists and Antagonists and the Role of Coactivators and Corepressors.

Editorial Reviews

3 Stars from Doody

There has been something akin to a "nuclear explosion" in our understanding of the molecular basis of hormone action. In the last five years, discovery of new receptors and the interaction of cofactors with nuclear receptors have challenged even the most sacred of endocrine dogmas. The editor should be congratulated in bringing together some of the most respected researchers in this area to write state-of-the-art papers in the area of molecular endocrinology. The goal is to go beyond a description of molecular biology, but to relate the knowledge we have gained into a physiological context. Graduate students and fellows interested in basic endocrinology would find this book a worthwhile investment with good diagrams and well-written summaries of some of the more confusing areas of this field. While the clinical endocrinologist may not have much use for this book, those doing research in any area of molecular endocrinology would find it extremely helpful as a reference for similar areas in which they may not be as well read. The book is divided into two sections. The first, "Growth Development and Metabolism," is a discussion of insulin, growth hormone, pit-l, thyroid hormone, and glucocorticoids. The second section is a discussion of the reproductive system. Most of the figures are extremely well done and educational, others -- "PowerPoint special" -- do not appear very crisp. There is some imbalance, as is inevitable, illustrated by three chapters on thyroid (no complaints here), but only one chapter on insulin (albeit very good), and no description of the knockout mouse and other mouse models of diabetes. In addition, it would have been useful to have one chapter summary ofall the steroid hormones, pointing out similarities and differences. A glossary of the cofactors (repressor/activators) and abbreviations would have been a unique and important addition. I love the book and will keep it handy when I sit down and decipher the new papers in molecular biology.

Roy E. Weiss

Shupnik (U. of Virginia Health Sciences Center) and a team of biochemists, endocrinologists, and geneticists, review animal and human model data to examine topics such as the molecular basis for growth, development, reproductive processes, and the hormonal regulation of gene expression. A more specific sampling of topics: thyroid hormone receptors and their multiple transcriptional roles; placental trophoblast cells<--> transcriptional regulation and differentiation; and the androgen receptor, androgen insensitivity, and prostate cancer. Annotation c. Book News, Inc., Portland, OR (booknews.com)

Booknews

Reviewer: Roy E. Weiss, MD, PhD (University of Chicago Medical Center)
Description: There has been something akin to a "nuclear explosion" in our understanding of the molecular basis of hormone action. In the last five years, discovery of new receptors and the interaction of cofactors with nuclear receptors have challenged even the most sacred of endocrine dogmas. The editor should be congratulated in bringing together some of the most respected researchers in this area to write state-of-the-art papers in the area of molecular endocrinology.
Purpose: The goal is to go beyond a description of molecular biology, but to relate the knowledge we have gained into a physiological context.
Audience: Graduate students and fellows interested in basic endocrinology would find this book a worthwhile investment with good diagrams and well-written summaries of some of the more confusing areas of this field. While the clinical endocrinologist may not have much use for this book, those doing research in any area of molecular endocrinology would find it extremely helpful as a reference for similar areas in which they may not be as well read.
Features: The book is divided into two sections. The first, "Growth Development and Metabolism," is a discussion of insulin, growth hormone, pit-l, thyroid hormone, and glucocorticoids. The second section is a discussion of the reproductive system. Most of the figures are extremely well done and educational, others — "PowerPoint special" — do not appear very crisp. There is some imbalance, as is inevitable, illustrated by three chapters on thyroid (no complaints here), but only one chapter on insulin (albeit very good), and no description of the knockout mouse and other mouse models of diabetes. In addition, it would have been useful to have one chapter summary of all the steroid hormones, pointing out similarities and differences. A glossary of the cofactors (repressor/activators) and abbreviations would have been a unique and important addition.
Assessment: I love the book and will keep it handy when I sit down and decipher the new papers in molecular biology.

Doody's Review Service

"The editor should be congratulated on bringing together some of the most respected researchers in this area to write state-of-the-art papers in the area of molecular endocrinology. . . Graduate students and fellows interested in basic endocrinology would find this book a worthwhile investment with good diagrams and well-written summaries of some of the more confusing areas of this field. . .I love the book and will keep it handy when I sit down and decipher the new papers in molecular biology."-Doody's Health Science Book Review Journal

From the Publisher