Role of the Liver in the Homeostasis of Calciferol Metabolism in the Dog*

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Abstract
To evaluate the role of the liver in the homeostasis of calciferol metabolism, the plasma concentrations of the major circulating vitamin D metabolites, 25-hydroxyvitamin D (25OHD), 24,25-dihydroxyvitamin D [24,25-(OH)2D], and 1,25- dihydroxyvitamin D [1,25-(OH)2D] were determined immediately proximal (portal vein) and immediately distal (hepatic vein) to the liver during steady state conditions in adult mongrel dogs. The liver handling of the parent compound, vitamin D (D), was evaluated by studying the uptake of a tracer dose of [3H]D3 during a single passage through the liver. The mean portal concentration of 25OHD was 14.31 ± 1.9 ng ml-1 in the portal vein and 13.27 ± 1.5 ng ml-1 in the hepatic vein, which represented an overall 7.2% extraction across the liver (P = NS). The liver handling of 25OHD was related to its prehepatic concentration, with an apparent predominance of 25OHD production over extraction at low portal vein concentrations, while the extraction exceeded the release at high portal vein 25OHD concentrations. The portal vein 24,25-(OH)2D concentration was 3.6 ± 0.5 ng ml-1, and the hepatic vein concentration was 2.8 ± 0.4 ng ml-1, which represented a transhepatic 24,25-(OH)2D extraction of 22% (P < 0.005). Positive correlations between plasma 25OHD and 24,25-(OH)2D were observed in both the portal (r = 0.9616; P < 0.001) and hepatic (r = 0.8820; P < 0.001) veins. Mean plasma 1,25-(OH)2D concentrations were 48.9 ± 2.9 and 39.2 ± 2.1 pg ml-1 in the portal and hepatic veins, respectively, representing a 19.7% or 9.6 ± 2.0 pg ml-1 (P < 0.001) extraction across the liver. The hepatic uptake of a single tracer dose of [3H]D3 was 60.5 ± 4.6%. It is proposed from the results of the present study that during steady state conditions in the dog, the liver tends to modulate the concentration of its own metabolite, 25OHD, while extracting significant amounts of D3, 24,25-(OH)2D, and 1,25-(OH)2D, indicating that the liver may also participate in the dynamic relationships regulating calciferol metabolism and homeostasis.

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