| Relationship between Expression of Sex Steroid Receptors and Structure of the Seminal Vesicles after Neonatal Treatment of Rats with Potent or Weak Estrogens Karin Williams, Jane S. Fisher, Katie J. Turner, Chris McKinnell, Philippa T.K. Saunders, and Richard M. Sharpe MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, Edinburgh, Scotland Abstract
In this study we evaluated the effect of manipulating the estrogen and androgen environment of the neonatal male rat on subsequent immunoexpression of sex steroid receptors in the seminal vesicles (SVs) at age 18 days. The aim was to establish to what extent such changes were associated with and predictive of changes in SV structure/composition. Treatments were either diethylstilbestrol (DES ; 10, 1, or 0.1 µg/injection) , ethinyl estradiol (EE ; 10 µg/injection) , tamoxifen (2 mg/kg/day) , flutamide (50 mg/kg) , a gonadotropin-releasing hormone antagonist (GnRHa ; 10 mg/kg) , genistein (4 mg/kg/day) , octylphenol (2 mg/injection) , or bisphenol A (0.5 mg/injection) . Compared with controls, treatment with DES (10 µg) induced loss of epithelial and stromal androgen receptor (AR) immunoexpression coincident with induction of stromal progesterone receptor (PR) immunoexpression and upregulation of stromal immunoexpression of estrogen receptor- (ER) . These changes were associated with gross distortion (increase) of the normal stromal:epithelial tissue proportions in the SVs. DES (1 µg) and EE induced similar but less pronounced changes, and DES (0.1 µg) had no noticeable effect. Tamoxifen and flutamide induced PR and slightly upregulated ER immunoexpression but had only a minor or no effect on AR expression and the stromal:epithelial ratio, though flutamide retarded normal development of the SVs. The latter was also evident in GnRHa-treated males, but otherwise this treatment had no effect on AR and PR immunoexpression. None of the foregoing treatments had any detectable effect on the immunoexpression of ERß in stromal or epithelial cells. The major treatment-induced changes in immunoexpression of AR, PR, and ER and lack of change in ERß were confirmed by Western blots of SV protein extracts. None of the three weak (environmental) estrogens tested caused any detectable change in sex steroid receptor immunoexpression or SV tissue composition. We conclude that treatment-induced loss of AR is a prerequisite for altered stromal:epithelial proportions in the SVs and that such loss is always associated with induction of PR and upregulation of ER ; the latter two changes are insufficient on their own to bring about such a change. Nevertheless, induction of PR expression was always associated with altered SV development and is a potentially useful marker because it is not normally expressed in male reproductive tissues. Key words: androgen-estrogen balance, androgen receptor, epithelium, estrogen receptor-, estrogen receptor-ß, progesterone receptor, stroma. Environ Health Perspect 109:1227-1235 (2001) . [Online 24 November 2001] http://ehpnet1.niehs.nih.gov/docs/2001/109p1227-1235williams/ abstract.html Address correspondence to R. M. Sharpe, MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, 37 Chalmers Street, Edinburgh EH3 9ET, Scotland, UK. Telephone: +44-131-229-2575. Fax: +44-131-228-5571. E-mail: r.sharpe@hrsu.mrc.ac.uk We are grateful to R. Deghenghi and Europeptides for their generous gift of GnRH antagonist and to J. MacDonald for expert assistance. This work was supported in part by the European Centre for the Ecotoxicology of Chemicals (ECETOC) , by a Strategic Research Fund Award from AstraZeneca plc and by contract QLK4-1999-01422 from the European Union. Received 5 February 2001 ; accepted 2 May 2001.
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