小児期における1,25-Dihydroxyvitamin D_3の作用機序並びにその受容体に関する研究

抄録

This article consists of the following 3 parts. 1) Metabolism of 1,25-(OH)_2-D_3 and Its Binding Mechanism in Familial Hypophosphatemic Vitamin D Resistant Rickets It is known that serum calcium concentration is not readily increased by vitamin D metabolites such as 1,25-(OH)_2-D_3 or 1α-(OH)-D_3 in familial hypophosphatemic vitamin D resistant rickets (VDRR). It has been reported that the same phenomenon is observed in the VDRR mouse known as a VDRR model. This abnormal biological response may be ascribed to abnormal interaction between 1,25-(OH)_2-D_3 and its receptor. We investigated receptors of 1,25-(OH)_2-D_3. No difference was observed in cytosol receptors in the duodenum between the control and VDRR mouse, but a significant decrease was observed in the nuclear uptake of 1,25-(OH)_2-D_3 by duodenal mucosal cells of the mice. 2) Effects of vitamin D_3 on Secretion of Insulin The effects of vitamin D_3 on the secretion of insulin was examined in perfusion tests using isolated pancreas of D-deficient rats. These results suggest that the decreased insulin release in the D-deficient rats is due to a reduction of intracellular Ca^<++> storage in the B cell, which we believe is a result of long term low plasma Ca levels in the D-deficient rats. 3) Biological Characterization of 1,25-(OH)_2-D_3 receptors in Chick Embryonal Duodenal Cytosol The binding activity of 1,25-(OH)_2-D_3 receptor in chick duodenal cytosol was maximal at the state of hatching. In addition, 1,25-(OH)_2-D_3 receptor before hatching might be composed of different forms of proteins corresponding to "fetal form".