Regulation of 1,25-dihydroxyvitamin d3 by calcium in the parathyroidectomized, parathyroid hormone-replete rat

Abstract

Parathyroid hormone (PTH) is a major stimulus for the renal production of 1,25-dihydroxyvitamin D₃ [1,25-(OH)₂D₃]. Elevated arterial blood ionized calcium ([Ca²⁺]) depresses serum 1,25-(OH)₂D₃ in nonparathyroidectomized rats even when serum PTH is maintained at high levels by infusion. However, suppression by [Ca²⁺] of endogenous PTH, causing the fall in 1,25-(OH)₂D₃, cannot be excluded. To determine whether [Ca²⁺] regulates 1,25-(OH)₂D₃ in the absence of a variation in PTH, we parathyroidectomized (PTX) rats (post-PTX calcium levels 2+] by infusing either 75 mM sodium chloride (control), 0.61 μmol/min of EGTA (EGTA), or calcium chloride at 0.61 μmol/min (low calcium) or 1.22 μmol/min (high calcium) for 24 h 5 days after surgery. Blood was then drawn from the rat through the arterial catheter. Compared with the control, [Ca²⁺] fell with EGTA, remained constant with the low-calcium infusion, and rose with the high-calcium infusion. 1,25-(OH)₂D₃ was correlated inversely with [Ca²⁺] in all four groups together (r = −0.635, n = 34, p < 0.001), within the control group alone (r = −0.769, n = 11, p < 0.002), and within the EGTA group alone (r = −0.774, n = 10, p < 0.003). Serum phosphorus, PTH, and arterial blood pH were not different in any group, and none correlated with serum 1,25-(OH)₂D₃. We conclude that 1,25-(OH)₂D₃ levels are regulated by [Ca²⁺] independently of serum PTH, phosphorus, and acid-base status, all of which support the hypothesis that [Ca²⁺] is a principal regulator of serum 1,25-(OH)₂D₃ in the rat.