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Estrogen receptor-? mediates diethylstilbestrol-induced feminization of the seminal vesicle in male mice.


ABSTRACT:

Background

Studies have shown that perinatal exposure to the synthetic estrogen diethylstilbestrol (DES) leads to feminization of the seminal vesicle (SV) in male mice, as illustrated by tissue hyperplasia, ectopic expression of the major estrogen-inducible uterine secretory protein lactoferrin (LF), and reduced expression of SV secretory protein IV (SVS IV).

Objectives

The present study was designed to evaluate the role of the estrogen receptor (ER) in this action by using ER-knockout (ERKO) mice.

Methods

Wild-type (WT), ER?-null (?ERKO), and ER?-null (?ERKO) male mice were treated with either vehicle or DES (2 ?g/day) on neonatal days 1-5. These mice were divided into two groups: In the first group, intact mice were sacrificed at 10 weeks of age; in the second group, mice were castrated at 10 weeks of age, allowed to recover for 10 days, treated with dihydrotestosterone (DHT) or placebo, and sacrificed 2 weeks later. Body weights and SV weights were recorded, and mRNA expression levels of Ltf (lactoferrin), Svs4, and androgen receptor (Ar) were assessed.

Results

In DES-treated intact mice, SV weights were reduced in WT and ?ERKO mice but not in ?ERKO mice. DES-treated WT and ?ERKO males, but not ?ERKO males, exhibited ectopic expression of LF in the SV. DES treatment resulted in decreased SVS IV protein and mRNA expression in WT males, but no effect was seen in ?ERKO mice. In addition, DES-treated ?ERKO mice exhibited reduced Svs4 mRNA expression but maintained control levels of SVS IV protein. In DES-treated castrated mice, DHT implants restored SV weights to normal levels in ?ERKO mice but not in WT mice, suggesting full androgen responsiveness in ?ERKO mice.

Conclusions

These data suggest that DES-induced SV toxicity and feminization are primarily mediated by ER?; however, some aspects of androgen response may require the action of ER?.

SUBMITTER: Walker VR 

PROVIDER: S-EPMC3339448 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Publications

Estrogen receptor-α mediates diethylstilbestrol-induced feminization of the seminal vesicle in male mice.

Walker Vickie R VR   Jefferson Wendy N WN   Couse John F JF   Korach Kenneth S KS  

Environmental health perspectives 20120124 4


<h4>Background</h4>Studies have shown that perinatal exposure to the synthetic estrogen diethylstilbestrol (DES) leads to feminization of the seminal vesicle (SV) in male mice, as illustrated by tissue hyperplasia, ectopic expression of the major estrogen-inducible uterine secretory protein lactoferrin (LF), and reduced expression of SV secretory protein IV (SVS IV).<h4>Objectives</h4>The present study was designed to evaluate the role of the estrogen receptor (ER) in this action by using ER-kno  ...[more]

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