TY - JOUR
T1 - Evidence that epithelial and mesenchymal estrogen receptor-α mediates effects of estrogen on prostatic epithelium
AU - Risbridger, Gail
AU - Wang, Hong
AU - Young, Peter
AU - Kurita, Takeshi
AU - Wong, Y. Z.
AU - Lubahn, Dennis
AU - Gustafsson, Jan Aake
AU - Cunha, Gerald
N1 - Funding Information:
The authors thank Dr. Ghanim Almahbobi for his help in the preparation and editing of the manuscript. This work was supported by grants to Risbridger (NH&MRC Program 973218), Lubahn (NIH ES 10535-01 and DAMD 17-98-1-8529), and Cunha (DK 47517, DK 52708, CA64872, CA 59831, CA 84294). This work was undertaken by G.P.R. during study leave taken at UCSF at the Cunha laboratory and completed at Monash University.
PY - 2001/1/15
Y1 - 2001/1/15
N2 - In combination with androgens, estrogens can induce aberrant growth and malignancy of the prostate gland. Estrogen action is mediated through two receptor subtypes: estrogen receptors α (ERα) and β (ERβ). Wild-type (wt) and transgenic mice lacking a functional ERα (αERKO) or ERβ (βERKO) were treated with the synthetic estrogen diethylstilbestrol (DES). DES induced prostatic squamous metaplasia (SQM) in wt and βERKO but not in αERKO mice, indicating an essential role for ERα, but not ERβ, in the induction of SQM of prostatic epithelium. In order to determine the respective roles of epithelial and stromal ERα in this response, the following tissue recombinants were constructed with prostatic epithelia (E) and stroma (S) from wt and ERKO mice: wt-S+wt-E, αERKO-S+αERKO-E, wt-S+αERKO-E, and αERKO-S+wt-E. A metaplastic response to DES was observed in wt-S+wt-E tissue recombinants. This response to DES involved multilayering of basal epithelial cells, expression of cytokeratin 10, and up-regulation of the progesterone receptor. Tissue recombinants containing αERKO-E and/or-S (αERKO-S+αERKO-E, wt-S+αERKO-E, and αERKO-S+wt-E) failed to respond to DES. Therefore, full and uniform epithelial SQM requires ERα in the epithelium and stroma. These results provide a novel insight into the cell-cell interactions mediating estrogen action in the prostate via ERα.
AB - In combination with androgens, estrogens can induce aberrant growth and malignancy of the prostate gland. Estrogen action is mediated through two receptor subtypes: estrogen receptors α (ERα) and β (ERβ). Wild-type (wt) and transgenic mice lacking a functional ERα (αERKO) or ERβ (βERKO) were treated with the synthetic estrogen diethylstilbestrol (DES). DES induced prostatic squamous metaplasia (SQM) in wt and βERKO but not in αERKO mice, indicating an essential role for ERα, but not ERβ, in the induction of SQM of prostatic epithelium. In order to determine the respective roles of epithelial and stromal ERα in this response, the following tissue recombinants were constructed with prostatic epithelia (E) and stroma (S) from wt and ERKO mice: wt-S+wt-E, αERKO-S+αERKO-E, wt-S+αERKO-E, and αERKO-S+wt-E. A metaplastic response to DES was observed in wt-S+wt-E tissue recombinants. This response to DES involved multilayering of basal epithelial cells, expression of cytokeratin 10, and up-regulation of the progesterone receptor. Tissue recombinants containing αERKO-E and/or-S (αERKO-S+αERKO-E, wt-S+αERKO-E, and αERKO-S+wt-E) failed to respond to DES. Therefore, full and uniform epithelial SQM requires ERα in the epithelium and stroma. These results provide a novel insight into the cell-cell interactions mediating estrogen action in the prostate via ERα.
KW - ERα
KW - Prostate
KW - Squamous metaplasia
KW - Tissue recombination
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U2 - 10.1006/dbio.2000.9994
DO - 10.1006/dbio.2000.9994
M3 - Article
C2 - 11150243
AN - SCOPUS:0035862917
SN - 0012-1606
VL - 229
SP - 432
EP - 442
JO - Developmental Biology
JF - Developmental Biology
IS - 2
ER -