Restoration of a phosphaturic response to parathyroid hormone in the immature rat

Recent studies have shown that immature rats display a diminished sensitivity to the phosphaturic effects of parathyroid hormone (PTH), and that the responsiveness to PTH increases with age. The attenuated phosphaturia may reflect an inability of the neonate to respond to the hormone because of functional immaturity of the developing kidney. Alternatively, PTH may actually inhibit tubular phosphate reabsorption in the neonate but, due to other phosphate conservation mechanisms, no phosphaturia occurs. Our objective was to determine whether a phosphaturic response to PTH would be elicited in immature rats during infusion of moderate amounts of phosphate (Pi). Clearance experiments were performed on 26 acutely thyroparathyroidectomized immature Wistar rats (3-5 wk of age) fed a normal Pi diet (0.63%). In response to infusion of either Pi (1 mol/min -100 g) (group I) or PTH (8.3 ng/ min 100 g) (group II) alone, the fractional excretion of phosphate rose minimally (from 0.01 ± 0.01% to 4.9 ± 1.9% and from 0.12 ± 0.12% to 2.9 ± 1.4% for groups I and II, respectively). However, when Pi and PTH were combined either Pi first followed by PTH (group III) or PTH first followed by Pi (group IV), the fractional excretion of Pi rose dramatically (from 0.01 ± 0.01 to 21.8 ± 3.5% and from 0.04 ± 0.04 to 27.7 ± 3.3% for groups III and IV, respectively). A significant increase in urinary cAMP excretion occurred during infusion of PTH even when Pi excretion was minimal, but there was no further increase in urinary cAMP during the combined infusion of Pi and PTH. These results indicate that a phosphaturic response to PTH can be elicited in immature rats during infusion of moderate amounts of phosphate, and that the phosphaturia is dissociated from the increase in urinary excretion of cAMP. Thus, the attenuated phosphaturic response to PTH seen in developing rats is not due to functional immaturity of the kidney, but rather could be attributed to other factors that promote Pi reabsorption and prevent the phosphaturic effect from being expressed.