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Journal of Endocrinology (2008) 197, 483-491       DOI: 10.1677/JOE-07-0470
© 2008 Society for Endocrinology
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Oestrogen and benign prostatic hyperplasia: effects on stromal cell proliferation and local formation from androgen

Clement K M Ho1,3, Jyoti Nanda1, Karen E Chapman2 and Fouad K Habib1

1 Prostate Research Group, University of Edinburgh Cancer Research Centre, Western General Hospital, 4th floor MRC Human Genetics Building, Crewe Road South, Edinburgh EH4 2XU, UK2 Endocrinology Unit, Room C 3.10, Centre for Cardiovascular Sciences, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK3 Clinical Biochemistry, Royal Infirmary of Edinburgh, University of Edinburgh, Little France Crescent, Edinburgh EH16 4SA, UK

(Correspondence should be addressed to F K Habib; Email: f.k.habib{at}ed.ac.uk)

The authors have no conflict of interest to declare.

Oestrogens have been implicated as a cause of benign prostatic hyperplasia (BPH). Previous animal studies led to the hypothesis that oestrogens can stimulate prostate growth, resulting in hyperplasia of the gland. In humans, the precise role of oestrogens in BPH pathogenesis is currently unclear. We investigated the direct effects of oestradiol on the proliferation of BPH-derived prostate cells in culture. Oestradiol (10–7 and 10–6 M) moderately increased the proliferation of stromal cells in culture; this stimulation was antagonised by anti-oestrogen ICI 182 780, indicating an oestrogen receptor (ER)-mediated mechanism. By contrast, oestradiol had no effects on the proliferation of epithelial cells in culture. Parameters that can determine the response of stromal cells to oestrogens, including expression of the two ER subtypes and aromatase activity, were investigated. ERβ expression in stromal cells in culture was demonstrated by immunohistochemistry and western blot analysis, and was confirmed by semi-quantitative RT-PCR showing higher expression of ERβ than ER{alpha} mRNA in stromal cells. Aromatase, the enzyme that converts androgen precursors to oestrogens, was also examined. Aromatase mRNA and activity were detected in stromal, but not epithelial cells in culture, suggesting a mechanism whereby oestrogen concentrations can be regulated in the BPH stroma. Taken together, these findings support the hypothesis that oestrogens play a role in the pathogenesis of BPH, a disease characterised predominantly by stromal overgrowth.







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