help button home button Endocrine Society Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
This version published online on October 26, 2006
Endocrinology, doi:10.1210/en.2006-0906
This Article
Right arrow Author Manuscript (PDF)
Right arrow All Versions of this Article:
148/2/566    most recent
Author Manuscript (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
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 MCPHERSON, S. J.
Right arrow Articles by RISBRIDGER, G. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by MCPHERSON, S. J.
Right arrow Articles by RISBRIDGER, G. P.

Submitted on July 7, 2006
Accepted on October 16, 2006

Essential role for estrogen receptor {beta} in stromal-epithelial regulation of prostatic hyperplasia

STEPHEN J. MCPHERSON, STUART J. ELLEM, EVAN R. SIMPSON, VLADIMIR PATCHEV, KARL-HEINRICH FRITZEMEIER, and GAIL P. RISBRIDGER*

Centre for Urological Research, Monash Institute of Medical Research, Monash University Clayton, Australia, 3168 (SJM, SJE, GPR); Prince Henry's Institute, Melbourne, Australia, 3168 (ERS)Schering AG, CRBA Gynecology and Andrology, Berlin, Germany, 13342 (VP, K-HF)

* To whom correspondence should be addressed. E-mail: gail.risbridger{at}med.monash.edu.au.

Estrogens, acting via estrogen receptors {alpha} and {beta} (ER{alpha} and ER{beta}), exert direct and indirect actions on prostate growth and differentiation. Previous studies using animal models to determine the role of ER{beta} in the prostate have been problematic because centrally mediated response to estrogen results in reduced androgen levels and prostatic epithelial regression, potentially masking any direct effects via ER{beta}. This study overcomes this problem by using the estrogen-deficient aromatase knockout (ArKO) mouse and tissue recombination to provide new insight into estrogen action on prostate growth and pathology.

Homo- and heterotypic ArKO tissue recombinants revealed stromal aromatase deficiency induced hyperplasia in normal prostatic epithelium due to disruption of paracrine interaction between stroma and epithelia. Treatment of tissue recombinants with an ER{beta} specific agonist demonstrated that stimulation of ER{beta} elicits anti-proliferative responses in epithelium that are not influenced by alterations to systemic androgen levels or the activation of ER{alpha}. Additionally, work performed with intact ArKO mice demonstrated that the administration of an ER{beta} specific agonist ablated pre-existing prostatic epithelial hyperplasia, while an ER{alpha} specific agonist did not. Therefore, failed activation of ER{beta}, resulting from local stromal aromatase deficiency, in conjunction with increased androgen levels, results in increased epithelial cell proliferation and prostatic hyperplasia. These data demonstrate essential and beneficial effects of estrogens that are necessary for normal growth of the prostate and distinguishes them from those that adversely alter prostate growth and differentiation. This highlights the potential of SERMS, rather than aromatase inhibitors, for the management of dysregulated prostate growth.
Key words: prostate • estrogen receptor {beta} • aromatase




This article has been cited by other articles:


Home page
 EndocrinologyHome page
M. Chen, I. Hsu, A. Wolfe, S. Radovick, K. Huang, S. Yu, C. Chang, E. M. Messing, and S. Yeh
Defects of Prostate Development and Reproductive System in the Estrogen Receptor-{alpha} Null Male Mice
Endocrinology, January 1, 2009; 150(1): 251 - 259.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
C. K M Ho, J. Nanda, K. E Chapman, and F. K Habib
Oestrogen and benign prostatic hyperplasia: effects on stromal cell proliferation and local formation from androgen
J. Endocrinol., June 1, 2008; 197(3): 483 - 491.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. A. Greenberg, S. Somme, H. E. Russnes, A. D. Durbin, and D. Malkin
The Estrogen Receptor Pathway in Rhabdomyosarcoma: A Role for Estrogen Receptor-{beta} in Proliferation and Response to the Antiestrogen 4'OH-Tamoxifen
Cancer Res., May 1, 2008; 68(9): 3476 - 3485.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
W. A. Ricke, S. J. McPherson, J. J. Bianco, G. R. Cunha, Y. Wang, and G. P. Risbridger
Prostatic hormonal carcinogenesis is mediated by in situ estrogen production and estrogen receptor alpha signaling
FASEB J, May 1, 2008; 22(5): 1512 - 1520.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
K. T Gray, J. L Short, E. R Simpson, and S. Ventura
The effects of targeted deletion of the aromatase enzyme on prostatic contractile responses to noradrenaline in mice
J. Endocrinol., December 1, 2007; 195(3): 495 - 502.
[Abstract] [Full Text] [PDF]

Home page
 J Mol EndocrinolHome page
G. P Risbridger, S. J Ellem, and S. J McPherson
Estrogen action on the prostate gland: a critical mix of endocrine and paracrine signaling
J. Mol. Endocrinol., September 1, 2007; 39(3): 183 - 188.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2006 by The Endocrine Society