Date of Award
Doctor of Philosophy
Timothy A. Reinhardt
Donald C. Beitz
Age-related changes often occur in factors involved in regulation of bone mineral metabolism, including 1,25-dihydroxyvitamin D[subscript]3 (1,25(OH)[subscript]2D[subscript]3) and parathyroid hormone (PTH) in plasma, 1,25(OH)[subscript]2D[subscript]3 receptors (VDR) and vitamin D[subscript]3-dependent calcium (Ca) binding proteins (CaBP-28K and CaBP-9K) in target tissues, and the 1[alpha],25-dihydroxyvitamin D-24-hydroxylase (24-hydroxylase);Response to exogenous 1,25(OH)[subscript]2D[subscript]3 was studied in 2.5- and 18-mo-old male and female rats. Additionally, response to dietary Ca deficiency was examined in one- and 18-mo-old male rats;Plasma 1,25(OH)[subscript]2D[subscript]3 concentrations decreased with age in rats of both genders. Abundance of the CaBP-28K and its mRNA in kidney, and CaBP-9K and CaBP-9K mRNA in intestine also decreased with age in both male and female rats. These decreases would be expected with low plasma 1,25(OH)[subscript]2D[subscript]3 concentrations. These data suggest increased renal catabolism of 1,25(OH)[subscript]2D[subscript]3 may be responsible for low plasma 1,25(OH)[subscript]2D[subscript]3 concentrations observed in the older animal. Most differences between males and female rats were found at 2.5 mo of age. Plasma PTH concentrations, plasma 1,25(OH)[subscript]2D[subscript]3 concentrations, 24-hydroxylase enzyme activity and 24-hydroxylase mRNA content in kidney, stimulation of intestinal 24-hydroxylase activity by treatment with 1,25(OH)[subscript]2D[subscript]3, abundance of 24-hydroxylase mRNA in intestine, and amount of CaBP-9K and CaBP-9K mRNA in intestine were greater in males compared with females of the same age. The lower plasma 1,25(OH)[subscript]2D[subscript]3 concentrations in females help to explain gender differences observed in the expression of several genes that are stimulated by 1,25(OH)[subscript]2D[subscript]3. In young male rats, renal VDR significantly declined as dietary Ca declined, but renal VDR in old rats was not affected by dietary Ca deficiency. Kidney VDR concentrations and expression of CaBP-28K mRNA responded similarly to the VDR protein in response to increasing age and depletion of dietary Ca. Dietary Ca deficiency caused a decrease in kidney 24-hydroxylase mRNA of 1-mo-old male rats but resulted in a slight increase or no change in kidney 24-hydroxylase mRNA from the already elevated amounts in 18-mo-old males. Intestinal CaBP-9K mRNA abundance increased in response to Ca deficiency only in young rats. Plasma 1,25(OH)[subscript]2D[subscript]3 concentrations were lower in old rats and increased much less in response to dietary Ca changes. (Abstract shortened by UMI.)
Digital Repository @ Iowa State University, http://lib.dr.iastate.edu/
Julie Ann Johnson
Johnson, Julie Ann, "Age, gender and diet effects on gene expression regulated by 1,25-dihydroxyvitamin D3 " (1993). Retrospective Theses and Dissertations. 10242.