Molecular Biology of the Parathyroid

aintaining extracellular calcium concentrations within a narrow range is critical for the survival of most vertebrates. PTH, together with vitamin D, responds to hypocalcemia to increase extracellu- M lar calcium levels, by acting on bone, kidney and intestine. The recent intro- duction of PTH as a major therapeutic agent in osteoporosis has directed renewed interest in this important hormone and in the physiology of the parathyroid gland. The parathyroid is unique in that low serum calcium stimulates PTH secretion. As hypocalcemia persists, there is also an increase in PTH synthesis. Chronic hypocalcemia leads to hypertrophy and hyper- plasia of the parathyroid gland together with increased production of the hormone. Phosphate is also a key modulator of PTH secretion, gene expres- sion and parathyroid cell proliferation. Understanding the biology of the parathyroid as well as the mecha- nisms of associated diseases has taken great strides in recent years. This book summarizes the molecular mechanisms involved in the function of the para- thyroid gland. The first chapter reviews the development of the parathyroid gland and the genes involved in this process as identified using genetically manipulated mice. Then the biosynthetic pathway of PTH from gene ex- pression to its intracellular processing and the sequences in the gene control- ling its transcription as well as those regulating mRNA processing, stability and translation are described.