Silver jubilee: 25 years of the first demonstration of the direct effect of phosphate on the parathyroid cell

Abstract

Although phosphorus is an essential element for life, it is not found in nature in its native state but rather combined in the form of inorganic phosphates (PO₄^3-), with tightly regulated plasma levels that are associated with deleterious effects and mortality when these are out of bounds. The growing interest in the accumulation of PO₄^3- in human pathophysiology originated in its attributed role in the pathogenesis of secondary hyperparathyroidism (SHPT) in chronic kidney disease. In this article, we review the mechanisms by which this effect was justified and we commemorate the important contribution of a Spanish group led by Dr. M. Rodríguez, just 25 years ago, when they first demonstrated the direct effect of PO₄^3- on the regulation of the synthesis and secretion of parathyroid hormone by maintaining the structural integrity of the parathyroid glands in their original experimental model. In addition to demonstrating the importance of arachidonic acid (AA) and the phospholipase A2-AA pathway as a mediator of parathyroid gland response, these findings were predecessors of the recent description of the important role of PO₄^3- on the activity of the calcium sensor-receptor, and also fueled various lines of research on the importance of PO₄^3- overload not only for the pathophysiology of SHPT but also in its systemic pathogenic role.

Keywords: CKD-MBD; Fosfato; Fósforo; Hormona paratiroidea; PTH; PTH receptor; Parathyroid; Parathyroid hormone; Paratiroides; Phosphate; Phosphorus; Receptor de la PTH.