Recent advances in genetic engineering and molecular biology have made it possible to disrupt specific genes in order to determine and better understand their function and clinical significance. In Gene Engineering in Endocrinology, Margaret Shupnik and a team of leading investigators review the most recent breakthroughs, emphasizing how studies of natural mutations and gene knockouts have illuminated endocrine processes. Using both animal and human model data, these authoritative researchers examine in depth the molecular basis of development, growth, and reproductive processes, the specific mutations that explain certain genetic syndromes, the hormonal regulation of gene expression (which affects the treatment of infertility and steroid-dependent cancers), and current research directions. When possible, molecular studies are compared with naturally occurring human and animal gene mutations to establish the difference between complete elimination of, or an altered, gene function.
Comprehensive and up-to-date, Gene Engineering in Endocrinology offers today's experimental and clinical endocrinologists, as well as reproductive biologists, a richly informative survey of what has already been accomplished with the genetic engineering of hormone processes and hormone-related genetic syndromes-research that promises powerful new experimental and therapeutic opportunities as this field continues it rapid development.

Klappentext

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.

Inhalt

Part I. Growth, Development, And Metabolism. Differential Cell Signaling and Gene Activation by the Human Growth Hormone Receptor: From Cell Surface to Cell Nucleus, Corinne M. Silva. Insulin Action: Molecular Mechanisms and Determinants of Specificity, Michael J. Quon and Simeon I. Taylor. Ets Transcription Factors: Nuclear Integrators of Signaling Pathways Regulating Endocrine Gene Expression and Carcinogenesis, Andrew P. Bradford and Arthur Gutierrez-Hartmann. Pit-1 Expression, Regulation, and Modulation of Multiple Pituitary Genes, Bryan R. Haugen, David F. Gordon, and William M. Wood. Subnuclear Trafficking of Glucocorticoid Receptors: General Mechanisms and Specific Recruitment to a Unique Target Site by Tethering to a DNA-Bound POU Domain Protein, Uma R. Chandran and Donald B. DeFranco. Thyroid Hormone Receptors and Their Multiple Transcriptional Roles, Paul M. Yen. Models of Resistance to Thyroid Hormone, Jung-Hsin Hsu and Gregory A. Brent. Thyroid Hormone Receptor Family Members: Homodimers, Heterodimers, and Mechanisms of Transcriptional Repression, Ronald N. Cohen and Fredric E. Wondisford. SF-1 and DAX-1: A Dynamic Duo in Endocrine Development, Mark W. Nachtigal, Debra Enyeart-Van Houten, and Holly A. Ingraham. Part II. Reproductive System. Gene Knockout Models to Study the Hypothalamus-Pituitary-Gonadal Axis, T. Rajendra Kumar and Martin M. Matzuk. Transgenic Approaches to Study Developmental Expression and Regulation of the Gonadotropin Genes, Katherine E. Graham and Malcolm J. Low. Molecular Events Defining Follicular Developments and Steroidogenesis in the Ovary, Joseph Orly. Regulation of Inhibin Subunit Gene Expression by Gonadotropins and cAMP in Ovarian Granulosa Cells, Abir Mukherjee and Kelly E. Mayo. Placental Trophoblast Cells: Transcriptional Regulation and Differentiation, Veronica Soloveva, Jiandie Lin, Grace T. Ma, and Daniel I. H. Linzer. Alternative Splicing of mRNAs for cAMP-Responsive Transcriptional Factors and Modulation of Transcription in the Testis, Philip B. Daniel and Joel F. Habener. The Androgen Receptor, Androgen Insensitivity, and Prostate Cancer, Michael J. McPhaul. Genetic Determination of Androgen Responsiveness, Terry R. Brown. Steroid Receptor Regulation by Phosphorylation and Cell Signaling Pathways, Nancy L. Weigel. Steroid Receptor Actions: Agonists and Antagonists and the Role of Coactivators and Corepressors, Derek A. Schreihofer, Eileen M. Resnick, and Margaret A. Shupnik. Index.