Localization of a negative vitamin D response sequence in the human growth hormone gene

Biochem Biophys Res Commun. 2002 Mar 22;292(1):250-5. doi: 10.1006/bbrc.2002.6641.


1,25-Dihydroxyvitamin D(3) [1,25(OH)(2) D(3)] exerts its biological effects by binding to the vitamin D receptor (VDR), which binds in turn to the vitamin D response elements located in the target gene's promoter. We have previously demonstrated that VDR binds in vitro with high affinity to the 5'-flanking sequence of the human growth hormone (hGH) gene. In this study, we analyzed the response to 1,25(OH)(2) D(3) of hGH-promoter constructs introduced by transfection into the MCF-7 human adenocarcinoma cell line. We found that the transcriptional activity of some of these constructs was markedly reduced by 1,25(OH)(2) D(3). Deletion analyses revealed that a 34-bp sequence located between positions -62 and -29 upstream of the transcription start site is sufficient for this repressive response. This conclusion was also confirmed by gel mobility shift assays. Our results indicate that vitamin D inhibits hGH gene transcription, directly or by interference with other transcription factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Calcitriol / pharmacology*
  • Electrophoretic Mobility Shift Assay
  • Gene Silencing*
  • Glutathione Transferase / genetics
  • Human Growth Hormone / genetics*
  • Humans
  • Molecular Sequence Data
  • Promoter Regions, Genetic
  • Receptors, Calcitriol / genetics
  • Receptors, Calcitriol / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Sequence Deletion
  • Tumor Cells, Cultured
  • Vitamin D Response Element*


  • Receptors, Calcitriol
  • Recombinant Fusion Proteins
  • Human Growth Hormone
  • Glutathione Transferase
  • Calcitriol