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Estrogen receptors (ERs) are typical members of the superfamily of nuclear receptors that mainly function as ligand-inducible transcription factors that bind chromatin, as homodimers, at specific response elements. A tight reciprocal coupling between rapid 'non-genomic' and 'genomic' ER actions may also occur in many physiological processes. ERs have long been evaluated for their roles in controlling the expression of genes involved in vital cellular processes such as proliferation, apoptosis, and differentiation. Therefore, given the various and pleiotropic functions of ERs, the dysregulation of their pathways contributes to several diseases such as the hormone-dependent breast; endometrial and ovarian cancers; and neurodegenerative diseases, cardiovascular diseases, and osteoporosis. In this printed edition of the Special Issue, "Molecular Pathways of Estrogen Receptor Action," promising results on understanding the mechanisms underlying ER-mediated effects in various pathophysiological processes are represented, covering different roles of ER pathways in the tumorigenesis, the resistance to endocrine therapy, the dynamics of 3D genome organization, and cross-talk with other signaling pathways. This Special Issue also provides insight into the emerging roles of estrogen-signaling pathways in lung cancer, the tumor microenvironment, and the immune system.]
The Textbook of Nephro-Endocrinology is the definitive translational reference in the field of nephro-endocrinology, investigating both the endocrine functions of the kidneys and how the kidney acts as a target for hormones from other organ systems. It offers researchers and clinicians expert, gold-standard analyses of nephro-endocrine research and translation into the treatment of diseases such as anemia, chronic kidney disease (CKD), rickets, osteoporosis, and, hypoparathyroidism. Investigates both the endocrine functions of the kidneys and how the kidney acts as a target for hormones from other organ systems Presents a uniquely comprehensive and cross-disciplinary look at all aspects of nephro-endocrine disorders in one reference work Clear translational presentations by the top endocrinologists and nephrologists in each specific hormone or functional/systems field
Endocrine Disruption and Human Health starts with an overview of what endocrine disruptors are, the issues surrounding them, and the source of these chemicals in the ecosystem. This is followed by an overview of the mechanisms of action and assay systems. The third section includes chapters written by specialists on different aspects of concern for the effects of endocrine disruption on human health. Finally, the authors consider the risk assessment of endocrine disruptors and the pertinent regulation developed by the EU, the US FDA, as well as REACH and NGOs. The book has been written for researchers and research clinicians interested in learning about the actions of endocrine disruptors and current evidence justifying concerns for human health but is useful for those approaching the subject for the first time, graduate students, and advanced undergraduate students. Provides readers with access to a range of information from the basic mechanisms and assays to cutting-edge research investigating concerns for human health Presents a comprehensive, translational look at all aspects of endocrine disruption and its effects on human health Offers guidance on the risk assessment of endocrine disruptors and current relevant regulatory considerations
In the classical signaling pathway, the estrogen receptor (ER) binds directly to estrogen response elements (EREs) to regulate gene transcription. The ER agonist, estradiol, activates ERE-mediated transcription, whereas the antagonist, ICI 182,780, induces repression. The non-classical ER signaling pathway was examined using an AP1-regulated promoter, which is controlled by the Jun/Fos family of transcription factors. In this model system, there was a reversal of ER action relative to that seen with the ERE reporter: estradiol caused suppression and ICI 182,780 stimulated transcription of the AP1 reporter. A functional interaction between Jun and ER was detected when tested in mammalian two-hybrid assays. Mutations were introduced into the DNA binding domain of mouse ERalpha to test the hypothesis that the non-classical pathway involves ER interaction with other proteins rather than direct binding to DNA. A mutation in the proximal box of the first zinc finger (E207A/G208A) eliminated ERE binding. This mutant was inactive using the ERE reporter but retained full activity on the AP1 reporter. To clarify the functional roles of these two signaling pathways in vivo we created a Non-classical Estrogen Receptor Knock-In (NERKI) mouse model by introducing the E207A/G208A mutation by targeted mutagenesis of embryonic stem cells. Unexpectedly, heterozygous NERKI females were infertile. The mice were anovulatory, and the ovaries exhibited disorganized thecal cells and lipid deposits in stromal cells. The uteri were enlarged with evidence of cystic endometrial hyperplasia. The mammary glands were underdeveloped, with decreased branching and lobuloalveolar development. Serum levels of progesterone were reduced, but levels of gonadotropins and estrogen were normal, suggesting a primary ovarian defect. Some aspects of the NERKI phenotype such as underdevelopment of mammary glands and lack of ovulation resemble the phenotype of ERalpha knock-out mice and likely reflect the dominant-negative activity of the ERE-binding-deficient ER mutant. However, the uterine features indicate excessive estrogen action, suggesting an important physiological role for the non-classical ER pathway in this tissue. Both in vitro and in vivo studies demonstrated that the ERE-binding-independent ER signaling is a part of normal actions of estrogens.
From our current knowledge, it is obvious that estrogen action in volves more than reproduction and fertility. Rather, estrogens affect and influence a number of other organ systems such as the immune, cardiovascular and central nervous system as well as the gastrointes tinal tract, urinary tract and skeleton. The importance of estrogens and estrogen receptor activity is appreciated from the spectrum of significant physiological dysfunctions that occur when there is a loss The participants of the workshop VI Preface of the hormone or the receptor activity. Loss of estrogen, however (for instance during menopause), occurs with time and results in a variety of clinical conditions. We know that the developmental loss of estrogen, as seen in clinical cases of aromatase gene mutations and experimental models, has dramatic effects in both men and women alike. The evidence that these effects are mediated through the estrogen receptor(s) is based on similar but not always identical phenotypes as observed in experimental animal models of estrogen receptor mutations as well as the single clinical case of an estrogen receptor alpha mutant patient. Developing an understanding of the spectrum of estrogen in a variety of tissues related to the condition of estrogen loss is a major and highly active clinical as well as basic scientific research area. Following the discovery of a second estrogen receptor and possible receptor ligand-independent activity as well as the genomic and non genomic actions of estrogen, it is clear that the mechanisms of the effects of estrogen are multifaceted.
Some investigators have hypothesized that estrogens and other hormonally active agents found in the environment might be involved in breast cancer increases and sperm count declines in humans as well as deformities and reproductive problems seen in wildlife. This book looks in detail at the science behind the ominous prospect of "estrogen mimics" threatening health and well-being, from the level of ecosystems and populations to individual people and animals. The committee identifies research needs and offers specific recommendations to decision-makers. This authoritative volume: Critically evaluates the literature on hormonally active agents in the environment and identifies known and suspected toxicologic mechanisms and effects of fish, wildlife, and humans. Examines whether and how exposure to hormonally active agents occursâ€"in diet, in pharmaceuticals, from industrial releases into the environmentâ€"and why the debate centers on estrogens. Identifies significant uncertainties, limitations of knowledge, and weaknesses in the scientific literature. The book presents a wealth of information and investigates a wide range of examples across the spectrum of life that might be related to these agents.
Molecular and Cellular Changes in the Cancer Cell,the latest volume in the Progress in Molecular Biology and Translational Science series, includes a comprehensive summary of the evidence accumulated thus far on the molecular and cellular regulation of the various adaptations taking place in response to exercise. This volume examines some of the latest advances, highlighting some of the most important molecular and cellular alterations and environmental influences that collectively cause a normal cell to become cancerous. Special emphasis is given to changes that take place at the molecular and cellular level. Comprehensive and up-to-date survey of current knowledge on the cancer cell Includes the latest advances and the most important molecular and cellular alterations and environmental influences collectively causing cells to become cancerous Written by leading experts in the field
The book provides a reference for years to come, written by world-renowned expert investigators studying sex differences, the role of sex hormones, the systems biology of sex, and the genetic contribution of sex chromosomes to metabolic homeostasis and diseases. In this volume, leaders of the pharmaceutical industry present their views on sex-specific drug discovery. Many of the authors presented at the Keystone Symposium on “Sex and gender factors affecting metabolic homeostasis, diabetes and obesity” to be held in March 2017 in Lake Tahoe, CA. This book will generate new knowledge and ideas on the importance of gender biology and medicine from a molecular standpoint to the population level and to provide the methods to study them. It is intended to be a catalyst leading to gender-specific treatments of metabolic diseases. There are fundamental aspects of metabolic homeostasis that are regulated differently in males and females, and influence both the development of diabetes and obesity and the response to pharmacological intervention. Still, most preclinical researchers avoid studying female rodents due to the added complexity of research plans. The consequence is a generation of data that risks being relevant to only half of the population. This is a timely moment to publish a book on sex differences in diseases as NIH leadership has asked scientists to consider sex as a biological variable in preclinical research, to ensure that women get the same benefit of medical research as men.
The first of its kind, this reference gives a comprehensive but concise introduction to epigenetics before covering the many interactions between hormone regulation and epigenetics at all levels. The contents are very well structured with no overlaps between chapters, and each one features supplementary material for use in presentations. Throughout, major emphasis is placed on pathological conditions, aiming at the many physiologists and developmental biologists who are familiar with the importance and mechanisms of hormone regulation but have a limited background in epigenetics.
The discovery of ER by Dr. Elwood Jensen exactly 60 years ago has not only led to the birth of a whole new vital nuclear receptor research field but also made a rapid, direct and lasting impact on the treatment and prevention of breast cancer. Since that landmark discovery, tremendous progress has been made in our understanding of the molecular functions of ER and development of targeted therapies against ER pathways for breast cancer treatment. However, there is currently no book available addressing these discoveries and recent advancement in a historical and systematic fashion. This book is intended to provide comprehensive, most up-to-date information on the history and recent advancement of ER and breast cancer by world renowned leaders in the field. These chapters include the history of the discovery of ER; physiological and pathological roles of ER; recent discovery of ER cistrome, transcriptome and its regulation of noncoding RNAs such as microRNAs and enhancer RNAs in breast cancer; development and clinical practices of the first targeted therapy Tamoxifen and other antiestrogens for breast cancer treatment; structural basis of ER and antiestrogen actions; molecular insights into endocrine resistance; the role of ER mutants, ER-beta and environmental estrogens in breast cancer; and emerging state-of-the-art therapeutic approaches currently in development to overcome treatment resistance and future perspectives. The book will provide undergraduate and graduate students, basic scientists and clinical cancer researchers, residents, fellows, as well as clinicians, oncology educators and the general public a thorough and authoritative review of these exciting topics.