This Article Full Text Full Text (PDF) All Versions of this Article: 147/1/191    most recent Author Manuscript (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 Taylor, R. A Articles by Risbridger, G. P. Search for Related Content PubMed PubMed Citation Articles by Taylor, R. A Articles by Risbridger, G. P.

17ß-Estradiol Induces Apoptosis in the Developing Rodent Prostate Independently of ER or ERß

Monash Institute of Reproduction and Development (R.A.T., P.C., G.P.R.), Monash University, Clayton, Victoria 3168, Australia; Department of Environmental and Molecular Toxicology (J.F.C.), North Carolina State University, Raleigh, North Carolina 27695; and Receptor Biology Section (J.F.C., K.S.K.), Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences/National Institutes of Health, Research Triangle Park, North Carolina 27709

Address all correspondence and requests for reprints to: Professor Gail P. Risbridger, Monash Institute of Medical Research, Monash University, 27–31 Wright Street, Clayton, Victoria 3168, Australia. E-mail: gail.risbridger{at}med.monash.edu.au.

Estrogens induce both proliferative and antiproliferative responses in the prostate gland. To date, antiproliferative effects of estrogens are generally considered to be due to systemic antiandrogenic actions. However, estrogen action mediated through estrogen receptor (ER) ß was recently suggested as another mechanism of induction of apoptosis in the prostate. This study aimed to explore the hypothesis that the antiproliferative effects of estrogen are directly mediated through ERß using a prostate organ culture system. We previously reported effects of 17ß-estradiol (E₂) using rat ventral prostate (VP) tissues, and adapted the system for culturing mouse tissues. In both rat and mouse models, estrogen-induced apoptosis was detected that was spatially and regionally localized to the epithelium of the distal tips. Using organ cultures of ER knockout (ERKO) and ßERKO prostates, we failed to demonstrate that apoptosis induced by E₂ was mediated through either receptor subtype. Activation of ER-selective ligands (ER, propyl pyrazole triol, ERß, diaryl-proprionitrile, and 5-androstane-3ß,17ß-diol) in organ culture experiments failed to induce apoptosis, as did the membrane impermeable conjugate E₂:BSA, discounting the possibility of nongenomic effects. Consequently, E₂ regulation of androgen receptor (AR) expression was examined and, in the presence of nanomolar testosterone levels, E₂ caused a specific reduction in AR protein expression in wild-type, ERKO, and ßERKO mice, particularly in the distal region where apoptosis was detected. This down-regulation of AR protein provides a possible mechanism for the proapoptotic action of E₂ that is independent of ERs or nongenomic effects.

This article has been cited by other articles:

				H. A. Harris Estrogen Receptor-{beta}: Recent Lessons from in Vivo Studies Mol. Endocrinol., January 1, 2007; 21(1): 1 - 13. [Abstract] [Full Text] [PDF]

				K. Dahlman-Wright, V. Cavailles, S. A. Fuqua, V. C. Jordan, J. A. Katzenellenbogen, K. S. Korach, A. Maggi, M. Muramatsu, M. G. Parker, and J.-A. Gustafsson International Union of Pharmacology. LXIV. Estrogen Receptors Pharmacol. Rev., December 1, 2006; 58(4): 773 - 781. [Full Text] [PDF]

				A Tivesten, E Bollano, H C Nystrom, C Alexanderson, G Bergstrom, and A Holmang Cardiac concentric remodelling induced by non-aromatizable (dihydro-)testosterone is antagonized by oestradiol in ovariectomized rats. J. Endocrinol., June 1, 2006; 189(3): 485 - 491. [Abstract] [Full Text] [PDF]

				R. S. Bhattacharyya, A. V. Krishnan, S. Swami, and D. Feldman Fulvestrant (ICI 182,780) down-regulates androgen receptor expression and diminishes androgenic responses in LNCaP human prostate cancer cells. Mol. Cancer Ther., June 1, 2006; 5(6): 1539 - 1549. [Abstract] [Full Text] [PDF]

				Q. Zhang and B. C. Paria Importance of Uterine Cell Death, Renewal, and Their Hormonal Regulation in Hamsters that Show Progesterone-Dependent Implantation Endocrinology, May 1, 2006; 147(5): 2215 - 2227. [Abstract] [Full Text] [PDF]