Chapter 25 - Parathyroid Hormone: Molecular Biology

Abstract

This chapter focuses on parathyroid hormone (PTH) gene, which is lo calized on the short arm of chromosome 11. The PTH gene is closely linked to the calcitonin gene and restriction enzyme analysis of the human PTH gene, as well as the use of denaturing gradient gel electrophoresis, demonstrated polymorphism in their cleavage products in different individuals The PTH gene is regulated by a number of factors. Calcitriol acts on the PTH gene to decrease its transcription, and this action is used in the management of patients with chronic renal failure. The main effect of calcium on PTH gene expression in vivo is for hypocalcemia to increase PTH mRNA levels, which seems likely to be posttranscriptional, but an in vitro transcriptional mechanism has been described whose physiological relevance remains to be determined. Phosphate also regulates PTH gene expression in vivo, and this effect appears to be independent of the effect of phosphate on serum calcium and 1,25(OH) 2 D 3 . The effect of phosphate is posttranscriptional, transacting parathyroid cytosolic proteins bind to a defined cis element in the PTH mRNA 3'-UTR, which determine the degradation of PTH mRNA by degrading enzymes and thereby the PTH mRNA half-life. The posttranscriptional effects of calcium and phosphate are the result of changes in the balance of these stabilizing and degrading factors on PTH mRNA. PTH mRNA binds to LC8, a member of the dynein family, which mediates the binding of mRNA to the microtubule apparatus of the parathyroid and may be important for the localization of PTH mRNA in the cell. Estradiol and progestins increase PTH mRNA levels, whose specific receptors are present in the parathyroids.