Chronic phosphorus supplementation decreases the expression of renal PTH/PTHrP receptor mRNA in rats

Dietary intake of high levels of phosphorus is known to increase serum levels of parathyroid hormone (PTH); however, how this increased serum PTH affects the action of PTH in major target tissues, particularly by kidney, remains unknown. In the present study, we therefore undertook to clarify this point in intact animals fed a high-P diet by examining various parameters of PTH action. Twelve weanling Wistar male rats were assigned randomly to two groups: a control group with dietary Ca:P = 1:1 and a high-P group (Ca:P = 1:3) fed the standard AIN-76 diet supplemented with P (0.5 and 1.5 g/100 g of diet). After 3 weeks of feeding, in the high-P diet group, we observed that serum Ca was lowered, without a difference in serum P, when compared to the control group. Excretion of urinary cAMP, an index of renal PTH action, was also decreased, with higher excretion of urinary P in those rats fed the high-P diet. In agreement with the decreased cAMP excretion, a clear reduction in PTH/PTH-related protein (PTHrP) receptor gene expression as estimated by Northern blotting was observed in the kidney, despite increased levels of serum PTH. Thus, the present study indicated that a high-P diet reduces PTH action in the kidney, though the serum PTH is increased.