This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted 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 Tschugguel, W. Articles by Huber, J. C. Search for Related Content PubMed PubMed Citation Articles by Tschugguel, W. Articles by Huber, J. C.

Differential Regulation of Proteasome-Dependent Estrogen Receptor and ß Turnover in Cultured Human Uterine Artery Endothelial Cells

Department of Obstetrics and Gynecology, Division of Gynecological Endocrinology and Reproductive Medicine, University of Vienna Medical School, General Hospital, A-1090 Vienna, Austria

Address all correspondence and requests for reprints to: Walter Tschugguel, M.D., University of Vienna Medical School, Department of Obstetrics and Gynecology, Division of Gynecological Endocrinology and Reproductive Medicine, General Hospital, Waehringer Guertel 18-20, A-1090 Vienna, Austria. E-mail: walter.tschugguel{at}akh-wien.ac.at.

Estrogen-induced loss of estrogen receptor (ER) expression limits estrogen responsiveness in many target cells. However, whether such a mechanism contributes to changes in vascular endothelial ER and/or ERß levels is unclear. Using RT-PCR assays, we did not find any regulation of ER or ERß mRNA expression in human uterine artery endothelial cell (HUAEC) nuclear extracts on stimulation with 17ß-estradiol for 1 or 2 h. By contrast, Western analysis on HUAEC extracts revealed that 17ß-estradiol was capable of down-regulating both ER and ERß protein starting 1 h after treatment, an effect that can be blocked by pretreatment with tamoxifen as well as with the proteasome inhibitor lactacystin. The proteolysis inhibitors insulin, cycloheximide, and puromycin impede ER, but not ERß, turnover. Ubiquitin, but not its competitive inhibitor methyl-ubiquitin, induces rapid turnover of both ERs in a cell-free system of MCF-7 and HUAEC extracts. We, thus, propose the existence of estrogen-induced ER degradation that serves to control physiological responses in an estrogen target tissue, i.e. human vascular endothelium, by down- regulating ER as well as ERß through different proteasomal uptake mechanisms.

This study was supported by Grant 8484 from the Oesterreichische Nationalbank (to W.T.).

Abbreviations: CHX, Cycloheximide; E₂, 17ß-estradiol; ER, estrogen receptor; FCS, fetal calf serum; HUAEC, human uterine artery endothelial cell; MeUb, methylated ubiquitin; PUR, puromycin; TAM, tamoxifen.

This article has been cited by other articles:

				K. Chang and Lubo Zhang Review Article: Steroid Hormones and Uterine Vascular Adaptation to Pregnancy Reproductive Sciences, April 1, 2008; 15(4): 336 - 348. [Abstract] [PDF]

				W. Dietrich, A. Haitel, G. Holzer, J. C. Huber, A. Kolbus, and W. Tschugguel Estrogen Receptor-{beta} Is the Predominant Estrogen Receptor Subtype in Normal Human Synovia Reproductive Sciences, October 1, 2006; 13(7): 512 - 517. [Abstract] [PDF]

				M. R. Meyer, E. Haas, and M. Barton Gender Differences of Cardiovascular Disease: New Perspectives for Estrogen Receptor Signaling Hypertension, June 1, 2006; 47(6): 1019 - 1026. [Full Text] [PDF]

				E Horner-Glister, M Maleki-Dizaji, C J Guerin, S M Johnson, J Styles, and I N H White Influence of oestradiol and tamoxifen on oestrogen receptors-{alpha} and -{beta} protein degradation and non-genomic signalling pathways in uterine and breast carcinoma cells J. Mol. Endocrinol., December 1, 2005; 35(3): 421 - 432. [Abstract] [Full Text] [PDF]

				R. R. Magness, T. M. Phernetton, T. C. Gibson, and D.-b. Chen Uterine blood flow responses to ICI 182 780 in ovariectomized oestradiol-17{beta}-treated, intact follicular and pregnant sheep J. Physiol., May 15, 2005; 565(1): 71 - 83. [Abstract] [Full Text] [PDF]

				P. Nancy and S. Berrih-Aknin Differential Estrogen Receptor Expression in Autoimmune Myasthenia Gravis Endocrinology, May 1, 2005; 146(5): 2345 - 2353. [Abstract] [Full Text] [PDF]

				W. X. Liao, R. R. Magness, and D.-b. Chen Expression of Estrogen Receptors-{alpha} and -{beta} in the Pregnant Ovine Uterine Artery Endothelial Cells In Vivo and In Vitro Biol Reprod, March 1, 2005; 72(3): 530 - 537. [Abstract] [Full Text] [PDF]

				A. E. Baker, V. M. Brautigam, and J. J. Watters Estrogen Modulates Microglial Inflammatory Mediator Production via Interactions with Estrogen Receptor {beta} Endocrinology, November 1, 2004; 145(11): 5021 - 5032. [Abstract] [Full Text] [PDF]

				C. Forster, S. Kietz, K. Hultenby, M. Warner, and J.-A. Gustafsson Characterization of the ER{beta}-/-mouse heart PNAS, September 28, 2004; 101(39): 14234 - 14239. [Abstract] [Full Text] [PDF]

				S. Suzuki and R. J. Handa Regulation of Estrogen Receptor-{beta} Expression in the Female Rat Hypothalamus: Differential Effects of Dexamethasone and Estradiol Endocrinology, August 1, 2004; 145(8): 3658 - 3670. [Abstract] [Full Text] [PDF]

				J. J. Pinzone, H. Stevenson, J. S. Strobl, and P. E. Berg Molecular and Cellular Determinants of Estrogen Receptor {alpha} Expression Mol. Cell. Biol., June 1, 2004; 24(11): 4605 - 4612. [Full Text] [PDF]

				V. M. Miller, D. J. Tindall, and P. Y. Liu Of Mice, Men, and Hormones Arterioscler Thromb Vasc Biol, June 1, 2004; 24(6): 995 - 997. [Full Text] [PDF]

				F. Barchiesi, E. K. Jackson, B. Imthurn, J. Fingerle, D. G. Gillespie, and R. K. Dubey Differential Regulation of Estrogen Receptor Subtypes {alpha} and {beta} in Human Aortic Smooth Muscle Cells by Oligonucleotides and Estradiol J. Clin. Endocrinol. Metab., May 1, 2004; 89(5): 2373 - 2381. [Abstract] [Full Text] [PDF]

				V. P. Korovkina, A. M. Brainard, P. Ismail, T. J. Schmidt, and S. K. England Estradiol Binding to Maxi-K Channels Induces Their Down-regulation via Proteasomal Degradation J. Biol. Chem., January 9, 2004; 279(2): 1217 - 1223. [Abstract] [Full Text] [PDF]

				O. M. Tirado, D. M. Selva, N. Toran, C. A. Suarez-Quian, M. Jansen, D. P. McDonnell, J. Reventos, and F. Munell Increased Expression of Estrogen Receptor {beta} in Pachytene Spermatocytes After Short-Term Methoxyacetic Acid Administration J Androl, January 1, 2004; 25(1): 84 - 94. [Abstract] [Full Text] [PDF]