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Evidence that estrogens directly alter androgen-regulated prostate development.
R A Jarred1, B Cancilla, G S Prins
1Monash Institute of Reproduction and Development, Monash University, Monash Medical Center, Clayton, Victoria, Australia.
Endocrinology
|August 31, 2000
Summary
Neonatal estrogen exposure directly inhibits prostate growth and alters development in vitro. These findings suggest estrogens have a direct impact on prostate gland development, independent of androgen levels.
Area of Science:
- Endocrinology
- Developmental Biology
- Urology
Background:
- Neonatal estrogen exposure permanently suppresses prostate growth and reduces androgen sensitivity in adulthood.
- The direct effects of estrogens on prostate development versus indirect effects via the hypothalamic-pituitary-gonadal axis remain unclear.
Purpose of the Study:
- To investigate the direct effects of estrogens on prostate development in vitro.
- To determine if estrogens directly impact prostate growth and differentiation independent of androgen levels.
Main Methods:
- Neonatal rat ventral prostates were microdissected and cultured with testosterone.
- Explants were treated with 17beta-estradiol or diethylstilbestrol in addition to testosterone.
- Unbiased stereology was used to quantify epithelial, stromal, and luminal volumes.
Main Results:
- Estrogens significantly reduced androgen-induced prostatic growth and altered differentiation.
- Proportion of epithelial cells and lumen decreased, while stroma increased.
- Branching pattern and ductal canalization were disturbed; stromal and epithelial differentiation were altered, independent of androgen receptor levels.
Conclusions:
- High doses of estrogens exert direct growth-inhibitory effects on prostate development in vitro.
- Estrogens directly disrupt prostate gland morphogenesis and differentiation.
- These direct effects may contribute to in vivo prostate alterations alongside indirect hypothalamic-pituitary-gonadal axis suppression.