This Article Full Text Full Text (PDF) 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 Alarid, E. T. Articles by Solodin, N. M. Search for Related Content PubMed PubMed Citation Articles by Alarid, E. T. Articles by Solodin, N. M.

Thyroid Hormone Is an Inhibitor of Estrogen-Induced Degradation of Estrogen Receptor- Protein: Estrogen-Dependent Proteolysis Is Not Essential for Receptor Transactivation Function in the Pituitary

Department of Physiology, University of Wisconsin, Madison, Wisconsin 53706

Address all correspondence and requests for reprints to: Elaine T. Alarid, Ph.D., Department of Physiology, University of Wisconsin Madison, 120 Service Memorial Institute, 1300 University Avenue, Madison, Wisconsin 53706. E-mail: alarid{at}physiology.wisc.edu.

Proteolysis by the 26S proteasome is an important regulatory mechanism that governs the protein stability of several steroid/nuclear receptors and that has been implicated in the control of receptor transcriptional activation function. Herein, we report that thyroid hormone can prevent estrogen-induced proteolysis of estrogen receptor- (ER) protein in lactotrope cells of the pituitary. The stabilization of ER protein by thyroid hormone represents a selective blockade against estradiol-stimulated degradation, because thyroid hormone (but not glucocorticoid) can protect estrogen-activated ER. Moreover, thyroid hormone treatment does not interfere with signal-induced proteolysis of a separate proteasome target, IB or ER proteolysis induced by ICI182780. Using thyroid hormone as a tool to inhibit ER proteolysis, we examined the effect of loss of this regulatory function on estrogen-induced transcriptional responses. Consistent with earlier reports, estrogen activation of an idealized estrogen response element reporter gene was inhibited. However, thyroid hormone did not prevent induction of prolactin gene expression or the ability of ER to stimulate proliferation. These results demonstrate that estrogen-induced proteolysis of ER is not a general requirement for receptor transcriptional activation function, and they demonstrate that proteolytic regulation is a means by which other endocrine factors can indirectly modulate ER activity.

This article has been cited by other articles:

				C. C Valley, N. M Solodin, G. L Powers, S. J Ellison, and E. T Alarid Temporal variation in estrogen receptor-{alpha} protein turnover in the presence of estrogen J. Mol. Endocrinol., January 1, 2008; 40(1): 23 - 34. [Abstract] [Full Text] [PDF]

				V. Duong, N. Boulle, S. Daujat, J. Chauvet, S. Bonnet, H. Neel, and V. Cavailles Differential Regulation of Estrogen Receptor {alpha} Turnover and Transactivation by Mdm2 and Stress-Inducing Agents Cancer Res., June 1, 2007; 67(11): 5513 - 5521. [Abstract] [Full Text] [PDF]

				N. Vasudevan and D. W. Pfaff Membrane-Initiated Actions of Estrogens in Neuroendocrinology: Emerging Principles Endocr. Rev., February 1, 2007; 28(1): 1 - 19. [Abstract] [Full Text] [PDF]

				M. T. Rae, O. Gubbay, A. Kostogiannou, D. Price, H. O. D. Critchley, and S. G. Hillier Thyroid Hormone Signaling in Human Ovarian Surface Epithelial Cells J. Clin. Endocrinol. Metab., January 1, 2007; 92(1): 322 - 327. [Abstract] [Full Text] [PDF]

				E. T. Alarid Lives and Times of Nuclear Receptors Mol. Endocrinol., September 1, 2006; 20(9): 1972 - 1981. [Abstract] [Full Text] [PDF]

				M. Fan, A. Park, and K. P. Nephew CHIP (Carboxyl Terminus of Hsc70-Interacting Protein) Promotes Basal and Geldanamycin-Induced Degradation of Estrogen Receptor-{alpha} Mol. Endocrinol., December 1, 2005; 19(12): 2901 - 2914. [Abstract] [Full Text] [PDF]

				C. C. Valley, R. Metivier, N. M. Solodin, A. M. Fowler, M. T. Mashek, L. Hill, and E. T. Alarid Differential Regulation of Estrogen-Inducible Proteolysis and Transcription by the Estrogen Receptor {alpha} N Terminus Mol. Cell. Biol., July 1, 2005; 25(13): 5417 - 5428. [Abstract] [Full Text] [PDF]

				J. Cho, D. Kim, S. Lee, and Y. Lee Cobalt Chloride-Induced Estrogen Receptor {alpha} Down-Regulation Involves Hypoxia-Inducible Factor-1{alpha} in MCF-7 Human Breast Cancer Cells Mol. Endocrinol., May 1, 2005; 19(5): 1191 - 1199. [Abstract] [Full Text] [PDF]

				X. Zhao, H. Lorenc, H. Stephenson, Y. J. Wang, D. Witherspoon, B. Katzenellenbogen, D. Pfaff, and N. Vasudevan Thyroid hormone can increase estrogen-mediated transcription from a consensus estrogen response element in neuroblastoma cells PNAS, March 29, 2005; 102(13): 4890 - 4895. [Abstract] [Full Text] [PDF]

				M. Fan, H. Nakshatri, and K. P. Nephew Inhibiting Proteasomal Proteolysis Sustains Estrogen Receptor-{alpha} Activation Mol. Endocrinol., November 1, 2004; 18(11): 2603 - 2615. [Abstract] [Full Text] [PDF]

				H.-W. Tsai, J. A. Katzenellenbogen, B. S. Katzenellenbogen, and M. A. Shupnik Protein Kinase A Activation of Estrogen Receptor {alpha} Transcription Does Not Require Proteasome Activity and Protects the Receptor from Ligand-Mediated Degradation Endocrinology, June 1, 2004; 145(6): 2730 - 2738. [Abstract] [Full Text] [PDF]