17β-Estradiol at low concentrations acts through distinct pathways in normal versus benign prostatic hyperplasia-derived prostate stromal cells

Irwin I. Park, Qiang Zhang, Victoria Liu, James M. Kozlowski, Ju Zhang, Chung Lee*

*Corresponding author for this work

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

The aim of this study was to identify differential responses to low concentrations of 17β-estradiol (E2) in primary stromal cell cultures derived from either normal organ donors or benign prostatic hyperplasia or hypertrophy (BPH) specimens. Furthermore, we sought to identify the potential mechanism of E2 action in these cell types, through either a genomic or nongenomic mechanism. Weinitially treated stromal cells derived from five normal prostates or five BPH specimens with low concentrations of E2 (0.001-1.0 nM) and analyzed their growth response. To determine whether genomic or nongenomic pathways were involved, we performed studies using specific estrogen receptor antagonists to confirm transcriptional activity or MAPK inhibitors to confirm the involvement of rapid signaling. Results of these studies revealed a fundamental difference in the mechanism of the response to E2. In normal cells, we found that a nongenomic, rapid E2 signaling pathway is predominantly involved, mediated by G protein-coupled receptor-30 and the subsequent activation of ERK1/2. In BPH-derived prostate stromal cells, a genomic pathway is predominantly involved because the addition of ICI 182780 was sufficient to abrogate any estrogenic effects. In conclusion, prostate stromal cells respond to far lower concentrations of E2 than previously recognized or examined, and this response is mediated through two distinct mechanisms, depending on its origin. This may provide the basis for new insights into the causes of, and possible treatments for, BPH.

Original languageEnglish (US)
Pages (from-to)4594-4605
Number of pages12
JournalEndocrinology
Volume150
Issue number10
DOIs
StatePublished - Oct 2009

ASJC Scopus subject areas

  • Endocrinology

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