Material from an the April 2000 National Institutes of Health (NIH) workshop held in Bethesda, Maryland, examines the role of the estrogen receptor in physiologic and pathologic processes involving multiple organ systems, discusses the potential for continued development of pharmacologic approaches

Ein multidisziplinärer Überblick über die aktuellen Themen und Zukunftstrends in der Erforschung von Naturstoffen mit Schwerpunkt auf pharmazeutischen und medizinischen Anwendungen.

The increasing awareness on the varied consequences of hypogonadism in distinct organs and systems has supported the notion of estrogens as systemic agents. This observation is congruent with the variety of tissues affected by - trogens when used in hormone therapy formulations on hypogonadic women. Apart from the genital tract and the breast, recognized as traditional targets for estrogens, the skeleton, the vascular tree, or the central nervous system, are good examples of territories that have demonstrated sensitivity to estrogens. This evidence has created great interest, as shown by the great amount of lit- ature that has been produced on the bene?ts and risks associated with the use of estrogens. In parallel to the clinical interest, basic research has improved our kno- edge on the complexities involved in estrogen action at the molecular level. Together with effects mediated through speci?c receptors, a concept that has been the mainstay of the interpretation of estrogen action for years, there is enough evidence to hold the notion of receptor-independent effects. The substantial advances in modern technology applied to research have helped in enlightening the particulars of this versatile action of estrogens. This more detailed knowledge on the sophisticated mechanism of action of estrogens has nourished the emergence of multiple hypotheses speculating with the p- sibility of manipulating estrogen action. The notion that a widely extended regulatory system of cell function, as it is the estrogen receptor machinery, might be modulated at wish has arisen as an attractive, although still elusive postulate.

Experimental and clinical researchers from a wide range of disciplines present a wealth of fresh scientific information on the biochemistry, molecular biology, pharmacology, and clinical activity of SERMs. The basic science chapters of the book focus-with an eye to the development of the ideal SERM-on the complex mechanisms of estrogen action, including ligand-dependent conformational changes in alpha and beta, and the recruitment of co-activators and co-repressors which modulate the estrogen receptor transcriptional activity and contribute to its crosstalk with growth factor signaling. The clinical presentation reviews the data accumulated on currently available SERMs, primarily tamoxifen and raloxifene, in cancer treatment and prevention, as well as their effects on the reproductive, vascular, skeletal, and central nervous systems. A tentative approach to menopause-related health issues is also provided for women with and without a previous diagnosis of localized breast cancer.

Written by the foremost authority in the field, this volume is a comprehensive review of the multifaceted phenomenon of hepatotoxicity. Dr. Zimmerman examines the interface between chemicals and the liver; the latest research in experimental hepatotoxicology; the hepatotoxic risks of household, industrial, and environmental chemicals; and the adverse effects of drugs on the liver. This thoroughly revised, updated Second Edition features a greatly expanded section on the wide variety of drugs that can cause liver injury. For quick reference, an appendix lists these medications and their associated hepatic injuries. Also included are in-depth discussions of drug metabolism and factors affecting susceptibility to liver injury.

Gene therapy, bioengineered skin, and other methods in advanced biology are revolutionizing the treatment of wounds. Written by experts in research and clinical practice, Cutaneous Wound Healing examines the current knowledge and emerging treatment methods. This volume explains the normal molecular and cellular functions that occur when a wound heals, as well as dysfunctional events, such as a chronic wound or an ulcer. Such dysfunctions signal an imbalance in the body, explained here along with possible treatments. The book's mini-atlas is an indispensable reference tool. Dermatologists, plastic surgeons, and general practitioners can benefit from this text.

This volume presents the evolution of the authors' ideas about estrogen action and its modulation by a new group of drugs called SERMs (Selective Estrogen Receptor Modulators). The pioneering SERMs OCo tamoxifen and raloxifene OCo are known to have saved the lives of millions of women around the world and improved the health of millions more. Estrogen is the central hormone of women's health and reproduction. The book is a journey through 40 years of discovery and success in advancing women's health, with the prospect of improved innovation through medicinal chemistry for the future.

Estrogens promote growth of certain breast endometrial cancers. Selective estrogen receptor modulators (SERMs), ligands that block the activity of estrogen in only selective tissues, allow to control the growth of these cancers while avoiding the many unwanted side effects associated with the use of antiestrogens. The goal of our work is to identify the mechanisms that control the activity of SERMs and to develop efficient high-throughput strategies for the identification of novel SERMs. SERMs exert their activities by binding to the two estrogen receptors, Era and ERb. Ligand binding changes the position of a-helix 12 (H12) in the ER ligand-binding domain and regulates the interaction of ERs with cellular coactivators and corepressors. Previously, we identified that the F-domain, a receptor-specific domain that follows H12, contributes to coactivator binding and specificity of Era but not ERb. We have continued these studies by analyzing the role of the F-domain in SERM-and corepressor binding and in modulating the transcriptional response to hormone. Moreover, we have identified and optimized a strategy to introduce fluorescence labels into H12 or the F-domain. These fluorescent receptors will allow us to monitor the dynamics and structural reorganization of ER upon SERM binding.

Supported by the latest scientific data, this book serves as a guide to the clinical assessment of women’s health during the second half of life (post-reproductive years), including approaches to the management of the most frequent age-related diseases and disorders and the most recent advances in treatment. In addition, it discusses preventive aspects of healthcare in post-reproductive women, identifying lifestyle measures to enhance healthy aging. By highlighting research gaps, it promotes the development of quick and easy-to-use assessment tools and predictive markers of age-related co-morbidities. As such, the book is a valuable resource for researchers and clinicians alike.

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