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Cotreatment with testosterone (T) and 17β-estradiol (E2) is an established regimen for inducing of prostatic intraepithelial neoplasia (PIN) and prostate cancer in rodent models. We previously used the pure antiestrogen ICI 182,780 (ICI) and bromocriptine, a dopamine receptor agonist, to inhibit PIN induction and systemic hyperprolactinemia in Noble rats and found that the carcinogenic action of T+E2 is mediated directly by the effects of E2 on the prostate and/or indirectly via E2-induced hyperprolactinemia. In this study, we delineate the specific action(s) of E2 and prolactin (PRL) in early prostate carcinogenesis by an integrated approach combining global transcription profiling, gene ontology, and gene-network mapping. We identified 2504 differentially expressed genes in the T+E2-treated lateral prostate. The changes in expression of a subset of 1990 genes (∼80%) were blocked upon cotreatment with ICI and bromocriptine, respectively, whereas those of 262 genes (∼10%) were blocked only by treatment with ICI, suggesting that E2-induced pituitary PRL is the primary mediator of the prostatic transcriptional response to the altered hormone milieu. Bioinformatics analyses identified hormone-responsive gene networks involved in immune responses, stromal tissue remodeling, and the ERK pathway. In particular, our data suggest that IL-1β may mediate, at least in part, hormone-induced changes in gene expression during PIN formation. Together, these data highlight the importance of pituitary PRL in estrogen-induced prostate tumorigenesis. The identification of both E2- and pituitary PRL-responsive genes provides a comprehensive resource for future investigations of the complex mechanisms by which changes in the endocrine milieu contribute to prostate carcinogenesis in vivo.

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Appalachian Americans are an underserved population with increased risk for diseases having strong genetic and environmental precursors. The purpose of this study is to understand the thoughts and perceptions of genetic research of Appalachian Americans residing in eastern Ohio prior to conducting a genetic research study with this population. A genetic survey was developed and completed by 180 participants from Marietta, Cambridge and East Liverpool, Ohio. The majority of respondents were Caucasian women with a median age of 37.5 years. We found that participants had a high interest in participating in 80 %, allowing their children to participate in 78 %, and learning more about genetic research studies (90 %); moreover, they thought that genetic research studies are useful to society (93 %). When asked what information would be useful when deciding to participate in a genetic research study, the following were most important: how environmental pollutants affect their genes and their child's genes (84 %), types of biological specimens needed for genetic research studies (75 %) and who will have access to their samples (75 %). Of the 20 % who responded that they were "unsure" about participating in a genetic research study, the leading reason was "I don't have enough information about genetic research to make a decision" (56 %). We also asked respondents to choose their preferred method for receiving genetic information, and the principal response was to read a brochure (40 %). Findings from this study will improve community education materials and dissemination methods that are tailored for underserved populations engaged in genetic research.

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