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Identification of a transcriptional fingerprint of estrogen exposure in rainbow trout liver

ABSTRACT: The goal of this study was to identify a set of hepatic genes regulated by ligand-dependent activation of the estrogen receptor in juvenile rainbow trout (Oncorhynchus mykiss) that can serve as a biomarker of estrogen exposure. A custom rainbow trout oligo DNA microarray, which contains probes targeting approximately 1450 genes relevant to carcinogenesis, toxicology, endocrinology and stress physiology was utilized to identify transcriptional “fingerprints” of in vivo dietary exposure to 17β-estradiol (E2), tamoxifen (TAM), estradiol + tamoxifen (E2+TAM), diethylstilbestrol (DES), dehydroepiandrosterone (DHEA), dihydrotestosterone (DHT) and cortisol (CORT). Estrogen exposure altered the expression of up to 49 genes involved in reproduction, immune response, cell growth, transcriptional regulation, protein synthesis and modification, drug metabolism, redox regulation and signal transduction. E2, DES and DHEA regulated 18 genes in common, mostly those associated with vitellogenesis, cell proliferation and signal transduction. Interestingly, DHEA uniquely regulated several complement component genes of importance to immune response. While the effect of TAM on E2-induced changes in gene expression was mostly antagonistic, TAM alone increased expression of VTG1 and other genes associated with egg development and immune response. Few genes responded to CORT treatment, and DHT significantly altered expression of only one gene targeted by the OSUrbt array. Hierarchical cluster and principal components analyses revealed distinct patterns of gene expression corresponding to estrogens and non-estrogens, though unique patterns could also be detected for individual chemicals. A set of estrogen-responsive genes has been identified that can serve as a biomarker of environmental exposure to xenoestrogens. Keywords: estrogen transcriptional profile, chemical transcriptional fingerprint

ORGANISM(S): Oncorhynchus mykiss

PROVIDER: GSE8226 | GEO | 2007/07/13

SECONDARY ACCESSION(S): PRJNA101151

REPOSITORIES: GEO

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Project description:ABSTRACT; The effects of DHEA were compared with those of DHT using gene expression array profiles in human LNCaP prostate cancer cells. LNCaP cells were exposed to DHEA (300 nM), DHT (300 nM), or vehicle for 48 hrs, and mRNA was isolated. mRNA expression was measured using Affymetrix HU-95 gene chips in 3 experiments performed on different dates. Gene expression values for the two treatment groups and control were sorted in ascending order on the p-values corresponding to a variance stabilized Hotelling test, which measured the extent of differential RNA expression between control and either hormone treatment. The top four genes with significant differential expression were S100 calcium binding protein, neurotensin, 24-dehydrocholesterol reductase, and anterior-gradient 2 homologue. Corresponding per comparison p-values were less than 3 x 10 -5. Nested tests of differential expression between DHEA and DHT treatment revealed significant differences (p < 0.01) for two of the four genes: the S100 calcium binding protein and neurotensin. The microarray findings were confirmed by quantitative RT-PCR. The top 83 genes found to exhibit differential expression were used in a pathway analysis. In general, DHT decreased expression of more genes involved in intercellular communication, signal transduction, nucleic acid binding and transport, and in structural components, such as myosin and golgin, than did DHEA. These data reveal consistent, measurable differences in gene expression patterns following treatment of LNCaP prostate cancer cells with DHEA versus DHT. The mechanisms underlying these observations, and the possible pathophysiological significance of these differences, remain to be determined. Experiment Overall Design: Three separate experiments were performed and labeled: 111502, 011403, and 022803. Three groups were run per experiment: Control, DHT or DHEA. Cells were exposed for 48 hr to 300 nM of DHT or DHEA. One Affymetrix HG_U95Av2 microarray chip per group was analyzed. The data was normalized by the "dchip" process.

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Identification of a transcriptional fingerprint of estrogen exposure in rainbow trout liver

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