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

Jose R. Weisinger, Murray J. Favus, Craig B. Langman, David A. Bushinsky*

*Corresponding author for this work

Research output: Contribution to journalArticle

65 Scopus citations

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 <7.0 mg/dl), inserted arterial and venous catheters, and then replaced PTH using an osmotic pump. We varied [Ca2+] 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.

Original languageEnglish (US)
Pages (from-to)929-935
Number of pages7
JournalJournal of Bone and Mineral Research
Volume4
Issue number6
DOIs
StatePublished - Dec 1989

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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