, 22:995 | Cite as

Selenoprotein P regulation by the glucocorticoid receptor



Maintenance of the antioxidant activity of selenoproteins is one potential mechanism of the beneficial health effects of selenium. Selenoprotein P is the primary selenium distribution protein of the body as well as the major selenium containing protein in serum. The transcriptional regulation of selenoprotein P is of interest since the extrahepatic expression of this gene has demonstrated differentiation-dependent expression in development as well as under different disease states. SEPP1 displays patterned expression in numerous tissues during development and the loss of SEPP1 expression has been observed in malignancy. In addition, factors that influence inflammatory processes like cytokines and their regulators have been implicated in selenoprotein P transcriptional control. Herein, we identify a retinoid responsive element and describe a mechanism where the glucocorticoid receptor negatively regulates expression of selenoprotein P. Luciferase reporter assays and quantitative PCR were used to measure selenoprotein P transcription in engineered HEK-293 cells. When stimulated with ecdysone analogs, selenoprotein P expression was increased with the use of a fusion transcription factor that contains the glucocorticoid receptor DNA binding domain, an ecdysone ligand-binding domain, and a strong transactivation domain as well as the retinoid X receptor. The native glucocorticoid receptor inhibited selenoprotein P transactivation, and selenoprotein P was further attenuated in the presence of dexamethasone. Our results may provide insight into a potential mechanism by which selenium is redistributed during development, differentiation or under conditions of critical illness, where glucocorticoid levels are typically increased.


Selenoprotein P Glucocorticoid receptor Glucocorticoids Antioxidant Retinoids 





Dimethyl sulfoxide




Glucocorticoid receptor


Forkhead box, class O1a


Glucocorticoid response element


Hepatocyte nuclear factor-4α


Polymerase chain reaction


Peroxisomal proliferator activated receptor-γ coactivator 1α


Ponasterone A


Retinoid responsive element


Retinoid X receptor


Selenoprotein P gene product


Selenoprotein P gene


Ecdysone-inducible fusion transcription factor



This work was supported by CA115616 (PJM) from the National Cancer Institute and P30 CA042014 to Huntsman Cancer Institute for support of core facilities. We thank Drs Hill and Burk for providing the anti-SelP antiserum. We also thank Drs Carol Lim, Michael Franklin, and the reviewers for their helpful suggestions on this article.


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Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  1. 1.Department of Pharmacology and ToxicologyUniversity of Utah, L.S. Skagg’s PharmacySalt Lake CityUSA

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