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The Vitamin D Receptor Represses Transcription of the Pituitary Transcription Factor Pit-1 Gene without Involvement of the Retinoid X Receptor

Department of Physiology, School of Medicine, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain

Address all correspondence and requests for reprints to: Roman Perez-Fernandez, Departamento de Fisiologia, Facultad de Medicina, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain. E-mail: fsropefe{at}usc.es.

Pituitary transcription factor-1 (Pit-1) plays a key role in cell differentiation during organogenesis of the anterior pituitary, and as a transcriptional activator for the pituitary GH and prolactin genes. However, Pit-1 is also expressed in nonpituitary cell types and tissues. In breast tumors, Pit-1 mRNA and protein levels are increased with respect to normal breast, and in MCF-7 human breast adenocarcinoma cells, Pit-1 increases GH secretion and cell proliferation. We report here that 1,25-dihydroxyvitamin D₃ [1,25-(OH)₂D₃] administration to MCF-7 cells induces a significant decrease in Pit-1 mRNA and protein levels. By deletion analyses, we mapped a region (located between –147 and –171 bp from the transcription start site of the Pit-1 gene) that is sufficient for the repressive response to 1,25-(OH)₂D₃. Gel mobility shift and chromatin immunoprecipitation assays confirmed the direct interaction between the vitamin D receptor (VDR) as homodimer (without the retinoid X receptor), and the Pit-1 promoter, supporting the view that Pit-1 is a direct transcriptional target of VDR. Our data also indicate that recruitment of histone deacetylase 1 is involved in this repressive effect. This ligand-dependent Pit-1 gene inhibition by VDR in the absence of the retinoid X receptor seems to indicate a new mechanism of transcriptional repression by 1,25-(OH)₂D₃.

NURSA Molecule Pages Link:

Nuclear Receptors:   VDR  |  RXRα

Coregulators:   HDAC1  |  HDAC2

Ligands:   Calcitriol  |  9-cis-Retinoic acid

This article has been cited by other articles:

				S. Seoane, I. Ben, V. Centeno, and R. Perez-Fernandez Cellular Expression Levels of the Vitamin D Receptor Are Critical to Its Transcriptional Regulation by the Pituitary Transcription Factor Pit-1 Mol. Endocrinol., July 1, 2007; 21(7): 1513 - 1525. [Abstract] [Full Text] [PDF]