Determination of the production and metabolic clearance rates of 1,25-dihydroxyvitamin D3 in the pregnant sheep and its chronically catheterized fetus by primed infusion technique.

Abstract

Because little is known regarding the determinants of plasma 1,25-dihydroxyvitamin D3(1,25(OH)2D3), or its fate in the fetus, we used a primed infusion technique, using physiologic amounts of high specific activity 3H-1,25(OH)2D3 to study the in vivo production rate (PR) and metabolic clearance rate (MCR) of 1,25(OH)2D3 in chronically catheterized maternal and fetal sheep during the last month of gestation (term = 145 d). The fetal MCR of 1,25(OH)2D3 was calculated at steady state, achieved within 2 h, and was found to be 2.53 +/- 0.19 mL/min (mean +/- SEM) compared to the maternal value of 15.9 +/- 0.94 mL/min. When expressed on a body wt basis, the fetal MCR of 1.22 +/- 0.09 mL/min/kg was more than 4-fold higher than the corresponding maternal value of 0.27 +/- 0.02 mL/min/kg. Measurement of endogenous plasma 1,25(OH)2D3 by RIA revealed mean fetal values of 89 +/- 10 pg/mL compared to the maternal value of 65 +/- 9 pg/mL. Fetal daily PR of 0.33 +/- 0.024 micrograms/d was 22% of the maternal PR of 1.49 +/- 0.11 micrograms/d. However, calculation of PR on a body wt basis revealed a fetal value of 0.159 +/- 0.012 micrograms/d/kg that was more than 6-fold higher than the maternal value of 0.025 +/- 0.002 micrograms/d/kg. Thus, fetal plasma concentrations of 1,25(OH)2D3 are sustained in the face of a high clearance rate of the hormone. The high MCR may be related to the high in vivo circulating concentrations of 1,25(OH)2D3, fetal to maternal placental transfer or target tissue uptake. In view of the high turnover of 1,25(OH)2D3, we suggest that this hormone has a biologic importance that warrants further investigation.