Vitamin D-dependent calcium-binding protein (CaBPs) in human fetuses: Comparative distribution of 9K CaBP mRNA and 28K CaBP during development

Abstract

The vitamin D-dependent calcium-binding protein (CaBP) cholecalcin or calbindin, has been used as a molecular marker of 1,25-dihydroxyvitamin D3 action. Mammals possess two CaBPs: a 9,000 mol wt (9K CaBP) and a 28,000 mol wt (28K CaBP). The distinct localization of each protein in the rat has been previously described with the aid of specific radioimmunoassays developed for each CaBP. Antibodies raised against the rat 28K CaBP can be used to detect this protein in a number of mammalian species including humans. In contrast, antibodies against rat 9K CaBP do not cross react with human 9K CaBP, but human 9K CaBP mRNA can be analyzed using a cDNA probe for rat 9K CaBP mRNA. Such a cross-hybridization between the rat cDNA probe and human CaBP mRNA was demonstrated by Northern analysis. We have documented the distribution and evolution of 28K CaBP and 9K CaBP mRNA in human tissues during fetal development from 14 to 32 wk of gestation. 28K CaBP was only present in kidney and cerebellum, and not detectable in duodenum. There was a 2-fold increase of 28K CaBP in the cerebellum between 14 and 24 wk of gestation. The 9K CaBP mRNA was unevenly distributed in human fetal tissues. 9K CaBP mRNA was present in classical vitamin D target tissues such as duodenum and placenta; high levels of 9K CaBP mRNA also were found in thymus and lung. These findings suggest a role for the hormone not only in the duodenum, placenta and kidney, but during the development of specific organs such as cerebellum, lung and thymus, and in agreement with many recent studies, point to a role of vitamin D in cellular differentiation and growth.