An acute chick kidney tubule model was used to evaluate the molecular specificity of steroids which act to inhibit kidney 25-hydroxyvitamin D3-1-hydroxylase and induce 25-hydroxyvitamin D3-24-hydroxylase enzyme activities. Such hydroxylase-regulatory activity was confirmed to the vitamin D family of secosteroids. Vitamin D3 per se was not active. Rather, expression of hydroxylase-regulatory activity required acquisition of a C-25 hydroxyl grouping. Of the metabolites tested, 25-hydroxyvitamin D3 demonstrated the greatest hydroxylase-regulatory activity. Metabolites of 25-hydroxyvitamin D3 which contained hydroxyl groups at carbon atoms 1, or 24, or both, were also active in regulating the kidney hydroxylase enzymes. The hydroxylase-regulatory action of 1,25-dihydroxyvitamin D3 was blocked by inhibitors of RNA or protein synthesis, implicating a requirement for de novo protein synthesis. It was suggested that the regulatory process involves both hydroxylase-enzyme synthesis and turnover as well as enzyme-level modulation of endogenous enzyme activities.
|Original language||English (US)|
|Number of pages||7|
|Journal||Journal of Biological Chemistry|
|State||Published - Dec 1 1980|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology