SYNTHESIS OF DIHYDROXYCHOLECALCIFEROLS IN MATERNAL AND FETAL ORGANS OF THE RAT IN THE LAST DAYS OF GESTATION

The in vitro synthesis of (3)H1,25(OH)(2)D-3 and (3)H24,25-(OH)(2)D-3 in different maternal (kidney and spleen), placental (maternal and fetal sides) and fetal (kidney, intestine, liver and skeleton) tissues and the relative contribution of each of these organs to total production was studied in the last six days of gestation in rats. On day 16, synthesis of both metabolites was higher in fetal tissues than in maternal kidney, and decreased as gestation advanced. On day 16, placental contribution represented more than 50% of the total production of (3)H1,25(OH)(2)D-3, while the maternal kidneys and the fetal tissues contributed only 16% and 26%, respectively. On day 18, the synthesis of (3)H1,25(OH)(2)D-3 by maternal placenta and fetal tissues was significantly reduced in comparison with that observed on day 16. Between days 16 and 19, the plasma concentrations of 1,25(OH)(2)D in mothers and fetuses were associated with the magnitude of its in vitro production. Starting on day 19, however, the in vitro production remained at the same level while the plasma concentration increased, suggesting lower utilization or lower catabolism of this metabolite. Similarly, the total synthesis of (3)H24,25(OH)(2)D-3 decreased on day 19. Between days 16 and 18, a higher synthesis of (3)H24,25(OH)(2)D-3 corresponded with lower plasma concentration of this metabolite suggesting greater utilization. In contrast, between days 19 and 21, the in vitro synthesis and plasma concentration of 24,25(OH)(2)D increased in paralel fashion. in summary we report the following findings: a) inhibition of the in vitro synthesis of (3)H1,25(OH)(2)D-3 and (3)H24,25(OH)(2)D-3 on day 19 of gestation in the rat; b) the contribution of each of the different maternal, placental and fetal tissues to the total synthesis of these metabolites in the last six days of gestation; and c) a paralelism between in vitro production and plasma concentration of both metabolites.