| The development of benign prostate hyperplasia, or BPH, is one of the most common disorders affecting the aging male population. Studies have found that approximately 60-80% of men between the ages of 60-69 years have evidence of BPH as determined at the time of autopsy. Though the development of BPH is typically a non-lethal occurrence, if not treated, BPH can lead to severe complications which have the potential to seriously endanger the patient's quality of life and overall health. As the prevalence of this prostate disorder is quite high in the male population, it is then not surprising that symptomatic presentation of BPH accounts for 1.7 million office visits and over 300,000 surgeries per year and an estimated cost of ;The aim of this study was to identify differential responses to low concentrations of 17beta-estradiol (E2) in primary stromal cell cultures derived from either normal organ donors, or from BPH specimens. Further, we sought to identify the potential mechanism of E2 action in these cell types, either through a genomic or non-genomic mechanism. We initially treated stromal cells derived from 5 normal prostates or from 5 BPH specimens with low concentrations of E2 (0.001nM-1.0nM) and analyzed their growth response. To determine whether genomic or nongenomic pathways were involved, we performed studies utilizing specific estrogen receptor antagonists to confirm transcriptional activity or MAP kinase 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 non-genomic, rapid E2 signaling pathway is predominantly involved, mediated by GPR30 and the subsequent activation of Erk1/2. In BPH-derived prostate stromal cells, a genomic pathway is predominantly involved, as 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 estrogenic 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. |
