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Molecular Biology of the Parathyroid (Molecular Biology Intelligence Unit)

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Maintaining 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 extracellular
calcium levels, by acting on bone, kidney and intestine. The recent introduction
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 hyperplasia
of the parathyroid gland together with increased production of the
hormone. Phosphate is also a key modulator of PTH secretion, gene expression
and parathyroid cell proliferation.

Understanding the biology of the parathyroid as well as the mechanisms
of associated diseases has taken great strides in recent years. This book
summarizes the molecular mechanisms involved in the function of the parathyroid
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 expression
to its intracellular processing and the sequences in the gene controlling
its transcription as well as those regulating mRNA processing, stability
and translation are described. Studies on the structure of PTH with correlations
to its function are presented and provide a starting point for understanding
the recognition of the PTH ligand by its receptor the PTH/PTHrP
or PTH1 receptor.
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