1-ALPHA,25-DIHYDROXYVITAMIN-D-3 RECEPTOR ONTOGENY IN FETAL RENAL DEVELOPMENT

We used immunohistochemical techniques to examine the distribution of 1 alpha,25-dihydroxyvitamin D-3 receptors (VDR) in developing rat and mouse kidneys and murine metanephric organ culture. In vivo, the patte rns of expression in the two species were similar despite the slight d ifference in gestational periods (rat, 22 days; mouse, 19 days). Start ing at gestational day 15, epitopes for VDR were found in cells of bra nching ureteral buds and in surrounding mesenchyme and at later develo pmental stages in glomerular visceral and parietal epithelial cells an d proximal and distal tubules (DT). Epitopes for the 28-kDa calcium-bi nding protein (calbindin D-28k) were found exclusively in DTs starting at gestational day 19. The pattern of VDR expression during in vitro nephrogenesis in serum-free murine metanephric organ culture parallele d that seen in vivo. At the time of explantation into organ culture (g estational day 13), VDR epitopes were not detected. By 3 days of in vi tro development, VDR expression was identical to that found in gestati onal day 15 metanephroi in vivo. VDR expression after 5 days of in vit ro development mirrored the pattern of gestational day 17 metanephroi in vivo. No calbindin D-28k epitopes were seen at any in vitro develop mental stage studied, We demonstrate for the first time that VDR are p resent in specific areas of the developing rat and mouse kidney early in gestation. Calbindin D-28k appears later in developing rat and mous e kidney and is distributed differently than the VDR. Metanephric orga n culture may be a useful model for studying the regulation and functi on of VDR during early renal development.