Molecular Biology of the Parathyroid. T. Naveh-Many (ed.), Kluwer Academic, New York, NY, USA, 2005. This book is one of a series of monographs and edited books that covers distinct areas of molecular biology in a single volume. The 196 pages of text are divided into 13 chapters. Individual chapters were contributed by different authors, which include many of the leading international experts in the field. The book represents a logical approach that ultimately gives a sequential and comprehensive description of the molecular biology of PTH. The first four chapters set the scene by discussing development of the parathyroid glands, the PTH gene, the PTH protein, and the physiological relationship between PTH and extracellular calcium. Thus, chapter 1 describes the embryological development of the parathyroid glands and the master genes involved in this process. Chapter 2 provides a detailed account of the cloning of the PTH gene and cDNA sequences, together with comparative analyses of their structures and sequences all set in a historical perspective. The third chapter includes an excellent analysis that details the structure-function relationships of the PTH protein and how a detailed understanding of protein structure may be used to design synthetic analogs of PTH. In chapter 4, the critical relationship between the calcium sensing receptor and the pathophysiological control of PTH secretion is clearly and concisely discussed. The following three chapters consider control of PTH gene expression. Chapter 5 discusses molecular mechanisms that determine how physiological changes in extracellular calcium and phosphate, which are mediated by dietary manipulation, regulate the half-life of PTH mRNA. Chapter 6 details approaches to study eukaryotic gene regulation using bioinformatics databases. The human PTH promoter is used as a working example for this chapter, and an analysis of potential transcription factor binding sites and regulatory sequences is included. The following chapter is a logical continuation because it includes a description of how 1,25(OH)2 vitamin D3, acting through the vitamin D receptor, regulates transcription of the PTH gene. This chapter concludes with physiological consideration of the impact of vitamin D deficiency on PTH expression and parathyroid cell proliferation. The next two chapters follow by discussing the treatment of secondary hyperparathyroidism and considering parathyroid gland hyperplasia. In chapter 8, treatment of secondary hyperparathyroidism with 1,25(OH)2 vitamin D3 is discussed, but the chapter focuses on the role of synthetic vitamin D analogs in this area. Specifically, this includes a good discussion of the rationale for the development of synthetic analogs, which selectively inhibit PTH gene expression and parathyroid cell proliferation but possess reduced calcemic potency. In this context, chapter 9 considers molecular mechanisms that underlie parathyroid cell proliferation and glandular hyperplasia and discusses additional therapeutic approaches to the control of parathyroid gland growth in renal failure. Chapters 10–12 extend the understanding of parathyroid gland growth and PTH gene regulation by giving a thorough and excellent description of the genes and molecular mechanisms responsible for parathyroid tumorigenesis, hyperparathyroidism, and hypoparathyroidism. These three chapters describe the relationship between molecular and clinical understanding of genetic disease processes in exemplary fashion. The final chapter is an important chapter because it clearly describes the phenotype of Pth-knockout mice and their response to dietary manipulation of calcium. The mouse studies are nicely set in context with other related mutant mouse models and with pathophysiological principles described elsewhere. In summary, the book includes a relatively succinct but wide discussion of PTH and the regulation of calcium homeostasis from a molecular genetic perspective. It achieves this admirably with good referencing. The chapters are well thought out and liberally illustrated with good figures. Nevertheless, there are reservations. As is often the case with multiauthored volumes, individual chapters vary in detail and organization, and some discuss noncontemporary issues at great length and appear out of date. These shortcomings have the effect of making the book appear rather disjointed. The preface indicates “the book is designed for students and teachers as well as scientists and investigators who wish to acquire an overview of the changing nature of the PTH field.” In this context, the editor is to be congratulated on the breadth of work covered and the production of an informative overview of PTH molecular biology set in an appropriate physiological context. Nevertheless, the book is inevitably superficial in parts and in some areas concentrates on older background studies rather than focusing on the current cutting edge. Despite these difficulties, this is an informative compilation that will provide a particularly valuable resource for graduate students and molecular endocrinologists undergoing PhD training, as well as having the potential to provide a core text for taught courses focusing on mineral metabolism in the bone, endocrine, or renal setting.
Read full abstract
Nov 20, 2006
P Björklund + 2
Open Access