help button home button Endocrine Society JCEM ENDO 08
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Shupnik, M. A.
Right arrow Articles by Laws, E. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shupnik, M. A.
Right arrow Articles by Laws, E. R., Jr.
The Journal of Clinical Endocrinology & Metabolism Vol. 83, No. 11 3965-3972
Copyright © 1998 by The Endocrine Society

Original Studies

Selective Expression of Estrogen Receptor {alpha} and ß Isoforms in Human Pituitary Tumors1

Margaret A. Shupnik, Leslie K. Pitt, Ann Y. Soh, Alice Anderson, M. Beatrice Lopes and Edward R. Laws, Jr.

Division of Endocrinology and Metabolism, Department of Internal Medicine (M.A.S., L.K.P., A.Y.S., A.A.); Department of Neuropathology (M.B.L.); and Department of Neurosurgery (E.R.L.), University of Virginia Health Science Center, Charlottesville, Virginia 22908

Address all correspondence and requests for reprints to: Margaret A. Shupnik, Ph.D., Box 578 HSC, University of Virginia, Charlottesville, Virginia 22908. E-mail: mas3x{at}virginia.edu

The physiological effects of estrogen on the pituitary, including cellular proliferation and regulation of hormone synthesis, are mediated by the nuclear estrogen receptor (ER). The ER acts as a dimer to modulate gene transcription and contains specific functional domains encoded in different exons. Two separate, but related, forms of the receptor (ER{alpha} and ERß) exist, with distinct tissue and cell patterns of expression. Additional ER isoforms, generated by alternative messenger ribonucleic acid (mRNA) exon splicing, have been defined in several tissues and are postulated to play a role in tumorigenesis or in modulating the estrogen response. We examined 71 human pituitary adenomas of varying phenotypes and 6 normal pituitary specimens for ER mRNA forms by RT-PCR and hybridization blotting analysis. All prolactinomas (n = 14) contained ER{alpha}, and several contained ERß (5 of 14) mRNA. In comparison, 6 tumors that expressed PRL and GH expressed ERß (4 of 6) more frequently than ER{alpha} (3 of 6). ERß mRNA was also found more frequently in null cell (8 of 24 ER{alpha} and 14 of 24 ERß) and gonadotrope (13 of 21 ER{alpha} and 18 of 21 ERß) tumors. Additionally, ERß was found in 4 of 6 tumors that contained only GH, although ER{alpha} was not observed in this tumor type. Expression of the two ER forms within a tumor type was overlapping, but some tumors contained only 1 isoform. Expression of ER{alpha} mRNA splice variants also varied with cell type. All normal pituitaries contained ER{alpha} deletions of exon 4, 5, and 7, whereas only 2 of 6 samples contained the exon 2 deletion variant. Although the same ER{alpha} mRNA variants were observed among the various tumor types, the proportion of specific splice variants expressed varied. For example, most ER-positive prolactinomas expressed ER{alpha} variants with deletions of exon 2, 4, or 5, whereas gonadotropin tumors preferentially expressed the ER{alpha} exon 7 deletion variant. A novel ERß mRNA splice variant, missing exon 2, was observed in a majority of all ERß-positive tumors. Immunoblotting analysis of ER{alpha} and ERß proteins supported the mRNA results. Because ER{alpha} and ERß have different biological responses to selective ER modulators, and the ER deletion variants have biological effects distinct from those of the full-length ER, expression of these isoforms may influence the biological properties of these tumors and affect their ability to respond to estrogen and antiestrogen therapies.




This article has been cited by other articles:


Home page
 Toxicol SciHome page
C. Montani, M. Penza, M. Jeremic, G. Biasiotto, G. La Sala, M. De Felici, P. Ciana, A. Maggi, and D. Di Lorenzo
Genistein is an Efficient Estrogen in the Whole-Body throughout Mouse Development
Toxicol. Sci., May 1, 2008; 103(1): 57 - 67.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. Cosma, J. Bailey, J. M. Miles, C. Y. Bowers, and J. D. Veldhuis
Pituitary and/or Peripheral Estrogen-Receptor {alpha} Regulates Follicle-Stimulating Hormone Secretion, Whereas Central Estrogenic Pathways Direct Growth Hormone and Prolactin Secretion in Postmenopausal Women
J. Clin. Endocrinol. Metab., March 1, 2008; 93(3): 951 - 958.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
N. Ben-Jonathan, C. R. LaPensee, and E. W. LaPensee
What Can We Learn from Rodents about Prolactin in Humans?
Endocr. Rev., February 1, 2008; 29(1): 1 - 41.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
J. D. Veldhuis, D. M. Keenan, and C. Y. Bowers
Peripheral estrogen receptor-{alpha} selectively modulates the waveform of GH secretory bursts in healthy women
Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2007; 293(4): R1514 - R1521.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
J. A. Arreguin-Arevalo, T. L. Davis, and T. M. Nett
Differential Modulation of Gonadotropin Secretion by Selective Estrogen Receptor 1 and Estrogen Receptor 2 Agonists in Ovariectomized Ewes
Biol Reprod, August 1, 2007; 77(2): 320 - 328.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
U. Ohnemus, M. Uenalan, J. Inzunza, J.-A. Gustafsson, and R. Paus
The Hair Follicle as an Estrogen Target and Source
Endocr. Rev., October 1, 2006; 27(6): 677 - 706.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
K. M.A. Dreijerink, K. W. Mulder, G. S. Winkler, J. W.M. Hoppener, C. J.M. Lips, and H.Th. M. Timmers
Menin Links Estrogen Receptor Activation to Histone H3K4 Trimethylation.
Cancer Res., May 1, 2006; 66(9): 4929 - 4935.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
J. D. Veldhuis, J. N. Roemmich, E. J. Richmond, and C. Y. Bowers
Somatotropic and Gonadotropic Axes Linkages in Infancy, Childhood, and the Puberty-Adult Transition
Endocr. Rev., April 1, 2006; 27(2): 101 - 140.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
E. J. Lee and J L. Jameson
Gene therapy of pituitary diseases
J. Endocrinol., June 1, 2005; 185(3): 353 - 362.
[Abstract] [Full Text] [PDF]

Home page
 Eur J EndocrinolHome page
P L Hanson, S J B Aylwin, J P Monson, and J M Burrin
FSH secretion predominates in vivo and in vitro in patients with non-functioning pituitary adenomas
Eur. J. Endocrinol., March 1, 2005; 152(3): 363 - 370.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
L. Xu, Q. Pan-Hammarstrom, A. Forsti, K. Hemminki, L. Hammarstrom, D. Labuda, J.-A. Gustafsson, and K. Dahlman-Wright
Human Estrogen Receptor {beta} 548 Is Not a Common Variant in Three Distinct Populations
Endocrinology, August 1, 2003; 144(8): 3541 - 3546.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
D. A. Schreihofer, D. F. Rowe, E. F. Rissman, E. M. Scordalakes, J.-a. Gustafsson, and M. A. Shupnik
Estrogen Receptor-{alpha} (ER{alpha}), But Not ER{beta}, Modulates Estrogen Stimulation of the ER{alpha}-Truncated Variant, TERP-1
Endocrinology, November 1, 2002; 143(11): 4196 - 4202.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
E. J. Lee, W. R. Duan, M. Jakacka, B. D. Gehm, and J. L. Jameson
Dominant Negative ER Induces Apoptosis in GH4 Pituitary Lactotrope Cells and Inhibits Tumor Growth in Nude Mice
Endocrinology, September 1, 2001; 142(9): 3756 - 3763.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
C. Tiffoche, C. Vaillant, D. Schausi, and M.-L. Thieulant
Novel Intronic Promoter in the Rat ER{alpha} Gene Responsible for the Transient Transcription of a Variant Receptor
Endocrinology, September 1, 2001; 142(9): 4106 - 4119.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
M. L. Nealen, K. V. Vijayan, E. Bolton, and P. F. Bray
Human Platelets Contain a Glycosylated Estrogen Receptor {beta}
Circ. Res., March 2, 2001; 88(4): 438 - 442.
[Abstract] [Full Text]

Home page
 Cancer Res.Home page
M. Campbell-Thompson, I. J. Lynch, and B. Bhardwaj
Expression of Estrogen Receptor (ER) Subtypes and ER{beta} Isoforms in Colon Cancer
Cancer Res., January 1, 2001; 61(2): 632 - 640.
[Abstract] [Full Text]

Home page
 Cancer Res.Home page
M. G. Ghosh, D. A. Thompson, and R. J. Weigel
PDZK1 and GREB1 Are Estrogen-regulated Genes Expressed in Hormone-responsive Breast Cancer1, 2
Cancer Res., November 1, 2000; 60(22): 6367 - 6375.
[Abstract] [Full Text]

Home page
 EndocrinologyHome page
D. A. Schreihofer, M. H. Stoler, and M. A. Shupnik
Differential Expression and Regulation of Estrogen Receptors (ERs) in Rat Pituitary and Cell Lines: Estrogen Decreases ER{alpha} Protein and Estrogen Responsiveness
Endocrinology, June 1, 2000; 141(6): 2174 - 2184.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. M. Resnick, D. A. Schreihofer, A. Periasamy, and M. A. Shupnik
Truncated Estrogen Receptor Product-1 Suppresses Estrogen Receptor Transactivation by Dimerization with Estrogen Receptors alpha and beta
J. Biol. Chem., March 15, 2000; 275(10): 7158 - 7166.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
J. F. Couse and K. S. Korach
Estrogen Receptor Null Mice: What Have We Learned and Where Will They Lead Us?
Endocr. Rev., June 1, 1999; 20(3): 358 - 417.
[Abstract] [Full Text]

Home page
 Cancer Res.Home page
E. Leygue, H. Dotzlaw, P. H. Watson, and L. C. Murphy
Expression of Estrogen Receptor {beta}1, {beta}2, and {beta}5 Messenger RNAs in Human Breast Tissue
Cancer Res., March 1, 1999; 59(6): 1175 - 1179.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 1998 by The Endocrine Society