Hypocalcemia, but not PTH or hypophosphatemia, induces a rapid increase in 1,25(OH)2D3 levels in rats.
This study determined whether acute decreases in plasma ionized calcium (Ca2+) levels regulate plasma 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] levels independent of changes in parathyroid hormone (PTH) secretion and plasma phosphate levels. Chronically catheterized rats were subjected to a hypocalcemic clamp (mean decrement of Ca2+ levels 0.38 +/- 0.04 mM), a rat PTH-(1-34) infusion, and a PTH vehicle infusion for 2 h. Plasma NH2-terminal immunoreactive PTH levels were elevated 3.2- and 8.7-fold during hypocalcemia and PTH infusion, respectively. Plasma phosphate decreased by 23 +/- 4 and 42 +/- 3% during hypocalcemia and PTH infusion, respectively. In response to hypocalcemia, plasma 1,25(OH)2D3 levels increased promptly, were significantly elevated by 15 min (56 +/- 23% increase), and continued to increase until the end of the experiment at 5 h (350 +/- 30% increase). In contrast, no changes in plasma 1,25(OH)2D3 levels occurred during the PTH infusion, but levels were elevated by 5 h, i.e., 3 h after the end of the infusion (360 +/- 20% increase). No significant changes in 25(OH)D3 or 24,25(OH)2D3 levels occurred in any protocol. Thus hypocalcemia rapidly elevates 1,25(OH)2D3 levels in rats, but the increase is not caused by elevated PTH secretion, hypophosphatemia, or elevated 25(OH)D3 levels. Furthermore, the increase in 1,25(OH)2D3 levels by hypophosphatemia does not occur rapidly. These studies show that there is a calcium-dependent mechanism that is independent of changes in PTH secretion and that results in the rapid elevation of plasma 1,25(OH)2D3 levels to counteract hypocalcemia.
Fox
J
J
Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana 70112.
D000818:Animals; D002117:Calcitriol / Q000097:blood*; D002118:Calcium / Q000097:blood; D006996:Hypocalcemia / Q000097:blood*; D008297:Male; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010710:Phosphates / Q000097:blood*; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D014807:Vitamin D / Q000378:metabolism
D010281:Parathyroid Hormone; D010710:Phosphates; D014807:Vitamin D; D002117:Calcitriol; D002118:Calcium