This book addresses and dissects the roles and crosstalk mechanisms for the 48 human nuclear receptors (NR) in human health and disease. After a State-of-the-Art introduction by an undisputed and celebrated field leader to provide an overview of the field and its significance, chapters are organized into six sections. The first three sections discuss NR roles in Reproduction & Development, Metabolism and Central Systems. These present to the reader our current understanding of NR signaling in the development and functioning of the reproductive system; the roles in the regulation of energy metabolism; and how NR signaling is more widely integrated into systemic functions from calcium flux to circadian rhythm. The subsequent three sections dissect how aberrant NR functions drive Cancer; how new insights into Genomic Interaction are helping to reveal how NR disruption drives disease; and finally, how Translational Efforts are exploiting this understanding from developing novel NR ligands to establishing how underlying genetic variation impacts NR function. 

Within these sections the chapters also illustrate emerging understanding of how the epigenome and non-coding genome combine to regulate NR function and impact dysfunction. Increasingly these insights cross-fertilize over cell and disease boundaries and it is unsurprising that NR are being explored in novel and new arenas such as the context of neurological disorders and depression. Thus, there is wide scope for re-purposing of licensed drugs and development of new NR-targeting therapies for a host of conditions and diseases.

This unique book brings together many of the leading figures in NR research from across the globe, to discuss emerging roles and their implications for human health and disease. It summarizes the state of the art and shows signposts for future research to further shape this influential field.

In 1890 a case of myxedema was treated in Lisbon by the implantation of a sheep thyroid gland with the immediate improvement in the patient’s condition. A few years later, medications for the then ill-explained condition of the menopause included tablets made from cow ovaries. In the first quarter of the 20th century the identification of vitamin D, and its sunlight driven production in skin, paved the way to the elimination of rickets as a major medical problem. Twenty years or so later, Sir Vincent Wigglesworth established the endocrine basis of developmental moulting in insects, arguably the most commonly performed animal behaviour on Planet Earth. A paradigm that would unify these disparate observations arose between 1985 and 1987 beginning with the identification of the glucocorticoid receptor and the nuclear receptor super-family. What follows is a timely and positive manifestation of the capacity, productivity and value of international human scientific endeavour. Based on intrigue, lively competition and cooperation a global effort has rapidly fostered a school of biology with widespread ramifications for the understanding of metazoan animals, the human condition and the state of the planet. This book is the first this century to try and capture the spirit of this endeavour, to depict where the field is now and to identify some of the challenges and opportunities for the future.

This book addresses and dissects the roles and crosstalk mechanisms for the 48 human nuclear receptors (NR) in human health and disease. After a State-of-the-Art introduction by an undisputed and celebrated field leader to provide an overview of the field and its significance, chapters are organized into six sections. The first three sections discuss NR roles in Reproduction & Development, Metabolism and Central Systems. These present to the reader our current understanding of NR signaling in the development and functioning of the reproductive system; the roles in the regulation of energy metabolism; and how NR signaling is more widely integrated into systemic functions from calcium flux to circadian rhythm. The subsequent three sections dissect how aberrant NR functions drive Cancer; how new insights into Genomic Interaction are helping to reveal how NR disruption drives disease; and finally, how Translational Efforts are exploiting this understanding from developing novel NR ligands to establishing how underlying genetic variation impacts NR function. 

Within these sections the chapters also illustrate emerging understanding of how the epigenome and non-coding genome combine to regulate NR function and impact dysfunction. Increasingly these insights cross-fertilize over cell and disease boundaries and it is unsurprising that NR are being explored in novel and new arenas such as the context of neurological disorders and depression. Thus, there is wide scope for re-purposing of licensed drugs and development of new NR-targeting therapies for a host of conditions and diseases.

This unique book brings together many of the leading figures in NR research from across the globe, to discuss emerging roles and their implications for human health and disease. It summarizes the state of the art and shows signposts for future research to further shape this influential field.

In 1890 a case of myxedema was treated in Lisbon by the implantation of a sheep thyroid gland with the immediate improvement in the patient’s condition. A few years later, medications for the then ill-explained condition of the menopause included tablets made from cow ovaries. In the first quarter of the 20th century the identification of vitamin D, and its sunlight driven production in skin, paved the way to the elimination of rickets as a major medical problem. Twenty years or so later, Sir Vincent Wigglesworth established the endocrine basis of developmental moulting in insects, arguably the most commonly performed animal behaviour on Planet Earth. A paradigm that would unify these disparate observations arose between 1985 and 1987 beginning with the identification of the glucocorticoid receptor and the nuclear receptor super-family. What follows is a timely and positive manifestation of the capacity, productivity and value of international human scientific endeavour. Based on intrigue, lively competition and cooperation a global effort has rapidly fostered a school of biology with widespread ramifications for the understanding of metazoan animals, the human condition and the state of the planet. This book is the first this century to try and capture the spirit of this endeavour, to depict where the field is now and to identify some of the challenges and opportunities for the future.