Steroid Hormone Action And Cancer

This volume is an outgrowth of a symposium held at the University of Michigan, Ann Arbor, Michigan, October 27-29, 1975. This symposium was organized to bring together basic scientists and clinicians for the purpose of exchanging new ideas and the latest information in the area of Steroid Hormone Action and Cancer. The design of the symposium included both formal plenary sessions and informal roundtable discussion groups, the chapters of this volume being drawn primarily from these proceedings. During the last quarter of a century considerable progress has been made toward understanding the molecular mechanisms in volved in steroid hormone action. It now appears that the mechan sim of action of the four major classes of steroid hormones is qualitatively similar. Research during the past decade has demonstrated steroid hormone receptors in a variety of normal and neoplastic tissues. Receptor-containing neoplasms have been shown to be hormone-dependent and undergo regression when treated with hormone antagonists. Natural and synthetic steroids also have been employed for many years to successfully treat various types of cancer, for example: estrogens, androgens and progestagens for breast cancer; estrogens and progestagens for prostatic carcinoma; progestagens for endometrial carcinoma; and corticoids for leu kemias. All of these neoplasms have now been found to possess receptors for the steroids empirically used in their treatment.

The series, Hormones in Health and Disease, was launched in 1993 to provide a scientific platform for investigators engaged in research on the biological actions of hormones and to anticipate relevance for their findings in clinical applications. The first volume of the series was dedicated to the discussion and understanding of molecular mechanisms by which steroid hormones influence target cells in normal and pathological conditions. With the diversity of information and the vast amount of literature on steroid hormone physiology, a more thorough treatment of Hormones and Cancer was identified as a timely topic. In this second volume in the series, Dr. Wayne V. Vedeckis has success fully undertaken the monumental task of editing the findings of the leading investigators in hormone and cancer research. Dr. Vedeckis brings to this project two decades of research experience in hormone action; he is actively engaged in elucidating hormone and cancer interrelations. It is a pleasure to welcome him to the series as an editor and congratulate him and all contribu tors in presenting this comprehensive treatise. The 20 chapters include discussions on contemporary topics relating control of cell division and signal transduction to the basic mechanisms of carcinogenesis by cloning patient genes, and recognizing the importance of steroid receptors in treatment protocols of various endocrine abnormalities.

During the last two decades, progress in steroid hormone research has resulted in the development of new approaches to contraception as well as diagnosis and treatment of endocrine disorders and cancers. Although significant advances have been made in the purification, characterization, immunochemistry and molecular biology of steroid receptors, the precise molecular mechanism of steroid hormone action has remained obscure. This book captures the detailed presentations made at the first conference on Steroid Receptors in Health and Disease held at Meadow Brook Hall, Oakland University in the fall of 1987. The purpose of this international con ference was to facilitate scientific exchange toward a better understand ing of the mode of action of steroid hormones. The scientific sessions consisted of poster presentations and state-of-the-art lectures, the latter of which make up this volume. The first chapter is meant to provide the reader with a more general background of the topics covered in the book, as well as to discuss certain theme-related issues that are either not yet well-established or accepted or are in the stage of infancy. It is hoped that this volume will serve as a useful treatise for students and investigators interested in basic and clinical aspects of biological regulation by steroid hormones. A task of this magnitude could not have been undertaken without the encouragement, advice and continued generous assistance of the members of the scientific committee. I am gratefully indebted to Drs.

The purpose of this book is to focus attention on recent developments in steroid and sterol hormone action. Many authors have generously contributed to the book. As a result, there is a great diversity of opinion! A majority of the chapters deal with steroid or sterol hormone receptors. This is not meant to imply that receptor-mediated mechanisms are the sole or even the most important mechanisms by which steroid hormones act in the cell. There is wealth of evidence showing that other, non-receptor events, are important also. Steroid hormone recep tor research and the study of nuclear events mediated by steroids are presently the most intensely studied aspects of sterol hormone action and our selection of topics reflects this trend. We have also included chapters on vitamin 0 sterols and thyroid hormone in the book, as there is pood evidence that these hormones act in a manner similar to other classical steroids. 1 IMMUNOCHARACTERIZATION OF THE NUCLEAR ACCEPTOR SITES FOR THE AVIAN OVIDUCT PROGESTERONE RECEPTOR A. GOLDBERGER, M. HORTON, T. C. SPELSBERG Department of Biochemistry and Molecular Biology, Mayo Clinic and Mayo Graduate School of Medicine, Rochester, MN 55905 INTRODUCTION It is well known that steroid hormones, certain vitamins and sterols, enter target cells and bind to specific protein receptors in the cyto plasm or nucleus (1-4). This binding is saturable, high affinity, and steroid specific.

Breast and prostate cancers are both hormone-dependent, at least in some stages of their progression. Hormonal manipulation represents an important therapeutic approach. Although most of breast and prostate cancers initially respond to hormone therapy, most tumors reinitiate to growth. Finally, hormone-resistant and metastatic breast and prostate cancers may develop. Thus, the challenge is the dissection of mechanisms by which steroid receptor signaling pathways continue to influence cell growth and invasiveness. Compelling evidence indicates that steroid hormones elicit non-genomic responses in extra-nuclear compartment of target cells. In this cellular location, steroid-coupled receptors rapidly recruit signaling effectors or scaffold proteins and activate multiple pathways leading to proliferation, survival, migration and invasiveness. The immediate challenge is the dissection of key events regulating the steroid response of target tissues to prevent progression and improve treatment of breast and prostate cancers.

Biological Activities of Steroids in Relation to Cancer covers the proceedings of the conference sponsored by the Cancer Chemotherapy National Service Center, National Cancer Institute, National Institutes of Health, and the U. S. Department of Health, Education and Welfare. The text focuses on the influence of steroids on medical approaches to the cure of cancer, including steroid chemistry, estrogen metabolism, and mammary cancer. The selection first offers information on steroids growth and cancer, advances in steroid chemistry, and the physiology and pharmacology of steroids affecting tumor growth. Discussions focus on rapid development of mammary cancer, pituitary functions, androgens, estrogens, and progestins. The book also ponders on the binding of steroid hormones by plasma proteins; the effects of steroids on the levels of the plasma 17-hydroxycorticosteroids and the serum protein-bound iodine; and the metabolism of dehydroisoandrosterone. The text evaluates studies on estrogen metabolism, biochemical parameters of estrogen action, and enzymatic transport of hydrogen by estrogenic hormones. The manuscript also elaborates on the fate of steroid estrogens in target tissues, effect of steroids on calcium dynamics, and steroids and experimental mammary cancer. The selection is a valuable source of information for readers interested in the use of steroids in treating cancer.