This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sheflin, L. G. Articles by Spaulding, S. W. Search for Related Content PubMed PubMed Citation Articles by Sheflin, L. G. Articles by Spaulding, S. W.

Androgen Regulates the Level and Subcellular Distribution of the AU-Rich Ribonucleic Acid-Binding Protein HuR Both in Vitroand in Vivo¹

Departments of Medicine (L.G.S., S.W.S.) and Physiology and Biophysics (S.W.S.), State University of New York and Veterans Affairs Western New York Healthcare System, Buffalo, New York 14215

Address all correspondence and requests for reprints to: Dr. Stephen W. Spaulding, Veterans Affairs Western New York Healthcare System, 3495 Bailey Avenue, Buffalo, New York 14215. E-mail: medspaul{at}acsu.buffalo.edu

HuR, a member of the ELAV family of AU-rich RNA-binding proteins, is present in a variety of tissues and is directly involved in stabilizing labile AU-rich messenger RNAs. We have found that treating the human HepG2 cell line with 10 nM dihydrotestosterone (DHT) for 48 h decreases the total level of HuR by 75%. DHT decreases both cytosolic and nuclear HuR levels in HepG2 cells, but increases HuR levels in polyribosomes by 325%. In BALB/c mice, HuR levels in the submaxillary salivary gland (SMG) and the kidney display a dramatic sexual dimorphism, but those in the spleen and thyroid do not. DHT (200 µg) causes total HuR levels in female SMG and kidney to fall progressively, whereas, conversely, orchiectomy of males causes HuR levels to rise in these two tissues by 800% and 200%, respectively. As an internal control we probed the same blots for AUF1, a destabilizing AU-binding protein, and confirmed our previous findings showing that the cytosolic p37 isoform of AUF1 shows the opposite responses of cytosolic HuR in the SMG, and that the level of AUF1 in the kidney does not respond to DHT. In polyribosomes from female mouse SMG, HuR levels doubled after 6 h of DHT, but decreased by 80% after 24- and 48-h DHT treatment. Thus, the total level of HuR is regulated in two different androgen-responsive systems, as is the shuttling of HuR between different subcellular compartments. As AUF1 is responsive to androgen in the mouse SMG, but not in the kidney, tissue-specific posttranscriptional regulation of AU-rich messenger RNA metabolism could be mediated in part by differential androgen-dependent regulation of HuR and AUF1.

This article has been cited by other articles:

				Z. Hu, B. G. Zimmermann, H. Zhou, J. Wang, B. S. Henson, W. Yu, D. Elashoff, G. Krupp, and D. T. Wong Exon-Level Expression Profiling: A Comprehensive Transcriptome Analysis of Oral Fluids Clin. Chem., May 1, 2008; 54(5): 824 - 832. [Abstract] [Full Text] [PDF]

				N. H. Ing, D. A. Massuto, and L. A. Jaeger Estradiol Up-regulates AUF1p45 Binding to Stabilizing Regions within the 3'-Untranslated Region of Estrogen Receptor {alpha} mRNA J. Biol. Chem., January 18, 2008; 283(3): 1764 - 1772. [Abstract] [Full Text] [PDF]

				L. Lu, L. Zheng, L. Viera, E. Suswam, Y. Li, X. Li, A. G. Estevez, and P. H. King Mutant Cu/Zn-Superoxide Dismutase Associated with Amyotrophic Lateral Sclerosis Destabilizes Vascular Endothelial Growth Factor mRNA and Downregulates Its Expression J. Neurosci., July 25, 2007; 27(30): 7929 - 7938. [Abstract] [Full Text] [PDF]

				N.S. Treister, S.M. Richards, T. Suzuki, R.V. Jensen, and D.A. Sullivan Influence of Androgens on Gene Expression in the BALB/c Mouse Submandibular Gland J. Dent. Res., December 1, 2005; 84(12): 1187 - 1192. [Abstract] [Full Text] [PDF]

				R. R. Manjithaya and R. R. Dighe The 3' Untranslated Region of Bovine Follicle-Stimulating Hormone {beta} Messenger RNA Downregulates Reporter Expression: Involvement of AU-Rich Elements and Transfactors Biol Reprod, October 1, 2004; 71(4): 1158 - 1166. [Abstract] [Full Text] [PDF]

				S. Yasuda, S. Wada, Y. Arao, M. Kogawa, F. Kayama, and S. Katayama Interaction between 3' Untranslated Region of Calcitonin Receptor Messenger Ribonucleic Acid (RNA) and Adenylate/Uridylate (AU)-Rich Element Binding Proteins (AU-Rich RNA-Binding Factor 1 and Hu Antigen R) Endocrinology, April 1, 2004; 145(4): 1730 - 1738. [Abstract] [Full Text] [PDF]

				D. Auboeuf, D. H. Dowhan, Y. K. Kang, K. Larkin, J. W. Lee, S. M. Berget, and B. W. O'Malley Differential recruitment of nuclear receptor coactivators may determine alternative RNA splice site choice in target genes PNAS, February 24, 2004; 101(8): 2270 - 2274. [Abstract] [Full Text] [PDF]

				C. Denkert, W. Weichert, S. Pest, I. Koch, D. Licht, M. Kobel, A. Reles, J. Sehouli, M. Dietel, and S. Hauptmann Overexpression of the Embryonic-Lethal Abnormal Vision-like Protein HuR in Ovarian Carcinoma Is a Prognostic Factor and Is Associated with Increased Cyclooxygenase 2 Expression Cancer Res., January 1, 2004; 64(1): 189 - 195. [Abstract] [Full Text] [PDF]

				L. B. Nabors, E. Suswam, Y. Huang, X. Yang, M. J. Johnson, and P. H. King Tumor Necrosis Factor {alpha} Induces Angiogenic Factor Up-Regulation in Malignant Glioma Cells: A Role for RNA Stabilization and HuR Cancer Res., July 15, 2003; 63(14): 4181 - 4187. [Abstract] [Full Text] [PDF]

				B. B. Yeap, D. C. Voon, J. P. Vivian, R. K. McCulloch, A. M. Thomson, K. M. Giles, M. F. Czyzyk-Krzeska, H. Furneaux, M. C. J. Wilce, J. A. Wilce, et al. Novel Binding of HuR and Poly(C)-binding Protein to a Conserved UC-rich Motif within the 3'-Untranslated Region of the Androgen Receptor Messenger RNA J. Biol. Chem., July 19, 2002; 277(30): 27183 - 27192. [Abstract] [Full Text] [PDF]