Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Effect of Ovarian Hormone on Gene Expression in Rhesus Dorsal Raphe Nucleus with Human U95A Affymetrix Chip

ABSTRACT: Small blocks of the midbrain containing the dorsal raphe nucleus was obtained from ovariectomized monkeys treated with placebo, estrogen, progesterone or estrogen plus progesterone for one month. The RNA was extracted and hybridized to the human U95A Affymetrix chip. Each chip represents one monkey. N=3 monkeys per treatment.

ORGANISM(S): Macaca mulatta

SUBMITTER: Arubala Reddy

PROVIDER: E-GEOD-16171 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Preliminary array analysis reveals novel genes regulated by ovarian steroids in the monkey raphe region.

Reddy Arubala P AP Bethea Cynthia L CL

Psychopharmacology 20050225 1

We hypothesize that ovarian hormones may improve serotonin neuron survival. We sought the effect of estradiol (E) and progesterone (P) on novel gene expression in the macaque dorsal raphe region with Affymetrix array analysis. Nine spayed rhesus macaques were treated with either placebo, E or E+P via Silastic implant for 1 month prior to euthanasia (n=3 per treatment). RNA was extracted from a small block of midbrain containing the dorsal raphe and examined on an Agilent Bioanalyzer. The RNA fro ...[more]

PMID: 15731897

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Project description:Bisphenol A (BPA) is primarily used to make polycarbonate plastic, with a global capacity of production exceeding 8 million tons per year. Biomonitoring studies with human urine, blood and tissue samples suggest that humans are subjected to widespread and continuous exposure to BPA. It has been well established that early life exposure to BPA predisposes the prostate gland to carcinogenesis later in life. However, it remains unknown if BPA exposure during adulthood induces benign or neoplastic pathology in the prostate. The main objective of the present study is to determine the effects of BPA exposures during adulthood on the prostate and to characterize the global transcriptional reprogramming underlying endocrine disruption by BPA. We elevated circulating levels of free BPA in Noble rats to the human-relevant internal dose range with BPA-filled Silastic implants while maintaining the physiological levels of testosterone (T) with T-filled implants. Cotreatment with T and 17β-estradiol (E2) was our reference regimen which induced preneoplastic and cancereous lesions. The T + low/high dose of BPA induced prostatic hyperplasia, low-grade prostate intraepithelial neoplasia (LGPIN) and intraepithelial infiltration of T-lymphocytes specifically in the lateral prostate (LP). Using microarray analysis, we delineated specific impacts of low and high dose of BPA (with the T-support) on the gene expression program in LPs. Hierarchical clustering revealed that the endocrine disrupting effects of T + low dose of BPA showed partial resemblance to those of T + high dose of BPA and T+E2. In contrast, the influence of T+ high dose of BPA on the LP transcriptome was completely different from those of T + E2. Further, IPA analysis of specific T+ low or high BPA gene signature identified a transcription factor, HNF4α, as a regulatory hub affecting a number of differentially expressed genes by BPA exposures. These findings suggest that the adult rat prostate is still venerable to the endocrine disrupting effects of BPA. Perhaps chronic exposure to low dose of BPA provides a niche comprising heightened cell proliferation, inflammatory responses and disrupted gene expression program, which favor the onset and development of prostatic benign or malignant diseases in men. Rat lateral prostates were collected from untreated control and treated groups [Testosterone (T) + Estradiol (E2), T + low dose Bisphenol A (low BPA) and T + high BPA] for RNA extraction and hybridization on Affymetrix microarrays. We sought to identify transcriptional signature of BPA exposures in the lateral prostate gland.

Dataset Information

Effect of Ovarian Hormone on Gene Expression in Rhesus Dorsal Raphe Nucleus with Human U95A Affymetrix Chip

Publications

Preliminary array analysis reveals novel genes regulated by ovarian steroids in the monkey raphe region.

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