The Insulin Like Growth Factors

This volume addresses a fundamental puzzle in biology and medicine, namely, how does tissue develop, repair and replace itself. The answer appears to lie in growth factors and their regulation. To thrive and survive we need growth factors and this book concentrates on two factors that are related to growth hormone. Growth hormone does not act directly on all tissues, but mediates many of its actions through the release of insulin-like growth factors from the liver. The growth factors were originally called somatomedins by McConaghey and Sledge (1), who discovered that they mediated growth-like effects of growth hormone. However, the factors were purified on the basis of their insulinomimetic actions on fat and muscle and it is their relationship to the insulin family of pep tides that now gives them their name (2,3) of insulin-like growth factors (IGFs). They mediate the actions of. growth hormone on the proteoglycan synthesis of cartilage and produce mitogenic effects in fibroblast cultures.

During the past decade, the continued interest in insulin-related growth factors has been documented by a plethora of research programs and publications focused on these growth factors. Both molecular and cellular biological techniques have improved and enabled investigators to study the properties of the growth factors in depth. This volume covers the molecular (genetic) aspects of the growth factors, their binding proteins and receptors, as well as those factors affecting their gene transcription and translation. In addition, aspects of the cellular action of these growth factors through their receptors and how this impacts normal cellular function are discussed. The book will provide valuable information for researchers in physiology, biology, endocrinology, and metabolism.

It has been over 40 years since the original report by Salmon and Daughaday demon strating that the ability of GH to stimulate sulfation of cartilage was mediated by a "sulfation factor. " In the ensuing decades, it has become apparent that this "sulfation factor activity" encompasses a complex system ofligands (IGFs), receptors, and carrier proteins that are, in tum, responsible for a wide array of cellular actions. The IGF system has been demonstrated to be critically involved in both intrauterine and postnatal growth, and to have important implications in cancer biology as well, owing to the ability of the IGFs to function in endocrine, paracrine, and autocrine modes and given the wide distri bution of IGFs in virtually every organ system. The contributions to The /GF System reflect the wide span of interest in the IGF system and its implications for normal and abnormal growth and metabolism. The chapters have been divided into four broad sections: I. Molecular biology of the IGF system; II. Bio logical actions of the IGFs; III. IGF physiology; and IV. Clinical aspects of the IGFs. We have made every effort to highlight the major contemporary themes in IGF biology, but as is inevitable in such a fast-moving field, perspectives will continue to change as new information is accumulated.

This Special Issue of Cells on “Insulin-Like Growth Factors in Development, Cancers and Aging” provides a collection of modern articles dealing with the role of insulin-like growth factors (IGF1) in cancer biology, aging and development. Featured articles explore basic and clinical aspects of the IGF1 system, including post-genomic analyses as well as novel approaches to target the IGF1 receptor (IGF1R) in oncology.

Insulin-like growth factors are ubiquitously expressed and are crucial for growth and function of almost all cells. Together with their binding proteins and receptors, they form a widely studied biological system involving many proteins and characterized by complex interactions. In addition to its significance in growth and development, the insulin-like growth factor system also has important roles in a wide variety of pathological states. This has led to interest in the therapeutic potential of insulin-like growth factors and their binding proteins as candidate drug targets. This comprehensive book contains current information on both basic science and clinical aspects of IGFs and their regulatory proteins, with emphasis on their relevance to cancer.

Traditionally, intercellular communication and the regulation of biological functions of the body have been considered the role of two major and distinct systems: the nervous system and the endocrine system. The classic nervous system transmitted its signal rapidly by using electrical currents, whereas the signals used by the endocrine system were hormones produced by endocrine glands which reached the target tissues via the blood stream. During the past few decades, it has become apparent that these systems of intercellular com munication are not distinct and the signal messenger molecules are not unique to one or the other system. Many classic endocrine hormones are found in and act on nervous tissues and evidence exists for their de novo synthesis by neural related tissues. An exciting development in this area is the possibility that insulin and insulin-like growth factors (IGF) are not only produced by neural tissues but also exert profound physiological and biochemical effects on these tissues. The area of investigation of CNS insulin and IGF has been expanding rapidly and the availability of this book complete with up-to-date reviews on the subject by leaders in the field allows other scientists to utilize the knowledge in planning and adapting the latest ideas for future experiments. In addition, the book provides a collection of up-to-date articles for teachers to be used for the latest instructional material. The first section of the book covers general aspects of insulin receptors and insulin action.

The book will detail the history, successes, and failures of targeted therapies for cancer, with a particular focus on IGF systems and cancer.

Annotation G.V. Sherbet provides insights into the signalling processes involved in morphogenesis and pathogenesis with emphasis on using the elements of the signalling cascades as targets for therapeutic deployment. The book focuses on the relationships and convergence of growth factors and their receptors in development and pathogenesis.