Title: Expression profiling of genes controlled by estradiol (E2) and/or nuclear estrogen receptors ER α and ER β
Abstract:The definition of the role of estrogen is a long-date scientific preoccupation. On the basis of the studies carried out in the last twenty years, it is now well accepted that estradiol and its cognate...The definition of the role of estrogen is a long-date scientific preoccupation. On the basis of the studies carried out in the last twenty years, it is now well accepted that estradiol and its cognate receptors are relevant transcription regulators in reproductive as well as non-reproductive tissues. Models of estrogen (E2) insufficiency (ArKO) and estrogen receptors (ER) dysfunction (ERKOs) have revealed new and unexpected roles of estradiol and its receptors both in female and male. The purpose of this study is to use mouse models of estrogen insufficiency (ArKO) and estrogen receptors dysfunction (ERKOs) to provide a genomic insight in the multiple and complex mechanisms defining estrogenic signaling to help understanding its role in physiological and pathological conditions. In particular the objective was to identify the genes responsive to estrogen signaling according to various possible mechanisms: 1) estrogen and estrogen receptordependent actions; 2) estrogen-independent and estrogen-receptor-dependent actions; 3) estrogen receptor-independent estrogen-dependent actions. To reach this aim, estrogen and estrogen receptors dependent genes expression profiling were performed by microarray analysis in ventral and dorso-lateral prostate and gonadal white adipose tissue from mouse models of impaired estrogen synthesis (ArKO) and ER action (ERKOs). The experimental and biological reproducibility of microarray data was first verified and confirmed providing a correlation between real-time PCR and microarrays in fold change measurements and in expression profiles across all tissues. The results obtained from the analysis of the expression profiles indicate that the classical and the non-genomic actions of estrogen are not to represent the main mechanisms of estrogenic signaling in prostate and adipose tissue. Conversely it appears that the estrogenic signaling in these tissues is exerted via estrogen receptors with an estrogen-independent mechanism of action. ERa appear to be the main mediator of the observed estrogenic effects, with mechanisms that differ according to the specific tissue. In ventral and dorso-lateral prostates, ERa seems to have inhibitory effects on transcription of target genes, supporting the hypothesis of its implication as a tumor suppressor in the prostate gland. Additional studies need to be performed to permit the identification of genes whose regulation can be directly modulated by ERs.Read More
Publication Year: 2009
Publication Date: 2009-01-01
Language: en
Type: dissertation
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