Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Benign prostate epithelial cell gene expression after four weeks of treatment with daily transdermal DHT or placebo gel

ABSTRACT: Significant increases in serum DHT do not increase intraprostatic levels of DHT, PSA, prostate volume, or prostate epithelial cell androgen-regulated gene expression in healthy men. Changes in serum androgen concentrations are not necessarily mimicked within the prostate. Custom Agilent 44K whole human genome expression oligonucleotide microarrays were used to profile benign prostate epithelium from twenty-seven men, twelve of which were treated for four weeks with daily transdermal DHT and 15 which were placebo gel treated controls. All samples were laser-capture microdissected and total RNA isolated and amplified prior to hybridization against a reference reference prostate cell line pool.

ORGANISM(S): Homo sapiens

SUBMITTER: Ilsa Coleman

PROVIDER: E-GEOD-20317 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Dihydrotestosterone administration does not increase intraprostatic androgen concentrations or alter prostate androgen action in healthy men: a randomized-controlled trial.

Page Stephanie T ST Lin Daniel W DW Mostaghel Elahe A EA Marck Brett T BT Wright Jonathan L JL Wu Jennifer J Amory John K JK Nelson Peter S PS Matsumoto Alvin M AM

The Journal of clinical endocrinology and metabolism 20101222 2

<h4>Context</h4>Concern exists that androgen treatment might adversely impact prostate health in older men. Dihydrotestosterone (DHT), derived from local conversion of testosterone to DHT by 5α-reductase enzymes, is the principal androgen within the prostate. Exogenous androgens raise serum DHT concentrations, but their effects on the prostate are not clear.<h4>Objective</h4>To determine the impact of large increases in serum DHT concentrations on intraprostatic androgen concentrations and andro ...[more]

PMID: 21177791

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Project description:Advancing age is associated with substantial increases in the incidence rates of common diseases affecting the prostate including benign prostatic hyperplasia (BPH) and prostate carcinoma. However, to date, there is no established molecular explanation for the age-dependent increases in these pathologies. The prostate is comprised of a functional secretory epithelium supported by a spectrum of cell types and structural elements comprising the stroma. As reciprocal interactions between epithelium and stromal constituents are essential for normal organogenesis and serve to maintain normal functions, discordance within the stromal could permit or promote disease processes. In this study we sought to identify aging-associated alterations in the mouse prostate that could influence pathology. We quantitated transcript levels in microdissected periglandular stroma from young (4 month-old) and old (20-24 month-old) C57BL/6 mice, and identified a significant change in the expression of 1259 genes (p<0.05). These included increases in transcripts encoding genes associated with inflammation (e.g., Ccl8, Ccl12), genotoxic/ oxidative stress (e.g., Apod, Serpinb5) and paracrine-acting proteins (e.g., Cyr61). The expression of several collagen genes (e.g., Col1a1 and Col3a1) exhibited age associated declines. By immunofluorescence and electron microscopy we determined that the aged prostate contains an abundant disorganized collagen matrix and a significant increase in inflammatory infiltrates comprised of macrophages, T cells and, to a lesser extent, B cells. These findings demonstrated that during normal aging the prostate stroma exhibits phenotypic and molecular characteristics plausibly contributing to the striking age associated pathologies affecting the prostate through oxidative stress and inflammatory cell damage. Custom Agilent 44K whole mouse genome expression oligonucleotide microarrays as well as custom mouse cDNA microarrays were used to measure transcript levels in microdissected periglandular stroma from young (4 month-old) and old (20-24 month-old) C57BL/6 mice. All samples were laser-capture microdissected and total RNA isolated and amplified prior to hybridization against a reference pool of normal adult mouse tissues.

Dataset Information

Benign prostate epithelial cell gene expression after four weeks of treatment with daily transdermal DHT or placebo gel

Publications

Dihydrotestosterone administration does not increase intraprostatic androgen concentrations or alter prostate androgen action in healthy men: a randomized-controlled trial.

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