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Molecular Mechanisms of Parathyroid Hormone Synthesis

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Diseases of the Parathyroid Glands

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Abstract

Parathyroid hormone (PTH) is central for the hormonal and cellular responses that determine mineral metabolism and bone strength. Small changes in serum calcium are sensed by the parathyroid G-protein coupled calcium-sensing receptor (CaR) and alter PTH secretion, gene expression, and if prolonged parathyroid cell proliferation. The major trigger for PTH secretion is a low extracellular calcium. PTH then binds to its receptor on its target tissues, the bone, and kidney to correct serum calcium. The parathyroid also responds to changes in serum phosphate (Pi), 1,25(OH)2 vitamin D (1,25D), and fibroblast growth factor-23 (FGF23). The regulation of PTH gene expression by dietary-induced changes in serum calcium, phosphate, and in chronic kidney failure is post-transcriptional and is mediated by the regulated binding of trans-acting proteins to a defined cis element in the PTH mRNA 3′-untranslated region (UTR). These protein–PTH mRNA interactions are orchestrated by the peptidylprolyl isomerase Pin1. In contrast, 1,25D decreases PTH gene transcription. This chapter discusses the molecular mechanisms of regulation of PTH gene expression that determine serum PTH levels and mineral metabolism.

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Authors and Affiliations

  1. Department of Nephrology, Hadassah Hebrew University Medical Center, Ein Karem, Jerusalem, 91120, Israel

    Tally Naveh-Many PhD & Morris Nechama PhD

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  1. Tally Naveh-Many PhD
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  2. Morris Nechama PhD
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Correspondence to Morris Nechama PhD .

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  1. , DEPTS BIOMED ENG & ENDOCRIN-METABOL, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, 44195-5036, Ohio, USA

    Angelo A. Licata

  2. Section of Nephrology, University of Illinois at, Department of Medicine, Associates in Nephrology, SC, Chicago, 60402, Illinois, USA

    Edgar V. Lerma

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Naveh-Many, T., Nechama, M. (2012). Molecular Mechanisms of Parathyroid Hormone Synthesis. In: Licata, A., Lerma, E. (eds) Diseases of the Parathyroid Glands. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-5550-0_1

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