Parathyroid hormone activation of the 25-hydroxyvitamin D3-1α-hydroxylase gene promoter

Holly L. Brenza, Christine Kimmel-Jehan, Frederic Jehan, Toshimasa Shinki, Shu Wakino, Hideharu Anazawa, Tatsuo Suda, Hector F. DeLuca

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Abstract

The DNA flanking the 5′ sequence of the mouse la-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 activity has been demonstrated by using a luciferase reporter gene construct transfected into a modified pig kidney cell line, AOK-B50. Parathyroid hormone stimulates this promoter-directed synthesis of luciferase by 17-fold, whereas forskolin stimulates it by 3-fold. The action of parathyroid hormone is concentration-dependent. 1,25-Dihydroxyvitamin D3 does not suppress basal promoter activity and marginally suppresses parathyroid hormone-driven luciferase reporter activity. The promoter has three potential cAMP-responsive element sites, and two perfect and one imperfect AP-1 sites, while no DR-3 was detected. These results indicate that parathyroid hormone stimulates 25-hydroxyvitamin D3-1α-hydroxylase by acting on the promoter of the 1α-hydroxylase gene.

Original languageEnglish
Pages (from-to)1387-1391
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number4
Publication statusPublished - 1998 Feb 17

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Keywords

  • Bone
  • Calcium
  • Cyclic AMP
  • Kidney
  • Vitamin D

ASJC Scopus subject areas

  • General

Cite this

Brenza, H. L., Kimmel-Jehan, C., Jehan, F., Shinki, T., Wakino, S., Anazawa, H., Suda, T., & DeLuca, H. F. (1998). Parathyroid hormone activation of the 25-hydroxyvitamin D3-1α-hydroxylase gene promoter. Proceedings of the National Academy of Sciences of the United States of America, 95(4), 1387-1391.