Regulation of expression of the Na+/H+ exchanger by thyroid hormone

Abstract

The Na+/H+ exchanger is a pH regulatory protein with a ubiquitous distribution in eukaryotic cells. Several isoforms of the Na+/H+ exchanger are known. The first isoform to be characterized and cloned, NHE1, is present on the plasma membrane of cells and functions to remove one intracellular proton in exchange for one extracellular sodium ion. It is involved in pH regulation, cell growth, differentiation, and cell migration. NHE1 is also involved in the cycle of damage that occurs in the heart with ischemic heart disease. Recent studies have shown that the Na+/H+ exchanger is regulated in response to thyroid hormone. Reduction in circulating thyroid hormone levels reduces the amount of both protein and mRNA of NHE1. Conversely, an elevation of thyroid hormone levels has the opposite effects. Transcriptional regulation of NHE1 expression has been demonstrated. The NHE1 promoter contains a TR alpha(1) binding site located between -841 to -800 bp. This element responds positively to TR alpha(1). This regulation of the NHE1 promoter by thyroid hormone is proposed to be responsible for postnatal changes in expression of the Na+/H+ exchanger.