PARATHYROID-HORMONE ACTIVATION OF THE 25-HYDROXYVITAMIN D-3-1-ALPHA-HYDROXYLASE GENE PROMOTER

The DNA flanking the 5' sequence of the mouse 1 alpha-hydroxylase gene has been cloned and sequenced. A TATA box has been located at -30 bp and aCCAAT box has been located at -79 bp. The gene's promoter activit y has br!en demonstrated by using a luciferase reporter gene construct transfected into a modified pig kidney cell line, AOK-B50. Parathyroi d hormone stimulates this promoter-directed synthesis of luciferase by 17-fold, whereas forskolin stimulates it by 3-fold. The action of par athyroid hormone is concentration-dependent. 1,25-Dihydroxyvitamin D-3 does not suppress basal promoter activity and marginally suppresses p arathyroid hormone-driven luciferase reporter activity. The promoter h as three potential cAMP-responsive element sites, and two perfect and one imperfect AP-1 sites, while no DR-3 was detected. These results in dicate that parathyroid hormone stimulates 25-hydroxyvitamin D-3-1 alp ha-hydroxylase by acting on the promoter of the 1 alpha-hydroxylase ge ne.