Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2005) 9 S26

BES2005 Symposia Symposium 6: Novel approaches for defining oestrogen action (4 abstracts)

Profiling in endometrium - genomic approaches to defining estrogen action

JG Moggs


Syngenta CTL, Macclesfield, UK.


Mammalian genome sequencing has driven the development of new -omic technologies that are capable of defining the genes, proteins and biological pathways that mediate cellular responses to endogenous and exogenous stimuli. We have used transcript profiling, which allows the expression levels of thousands of genes to be measured simultaneously, to define the molecular mechanism of 17beta-estradiol (E2) signalling in vivo, using the rodent uterotrophic assay as a model experimental system. Hierarchical clustering and functional annotation of E2-responsive genes, and comparison of temporal gene expression changes with histological alterations, revealed that uterine growth and maturation is driven by a complex, multi-stage transcriptional cascade. This program begins with the induction of genes involved in transcriptional regulation and signal transduction, and is followed, sequentially, by the regulation of genes involved in protein biosynthesis, cell proliferation and epithelial cell differentiation.

The definition of the transcriptional programme for the potent physiological estrogen, E2, provides a reference for the analysis of mechanisms by which xenoestrogens exert their effects. The xenoestrogen group of endocrine disruptors have the potential to cause reproductive and developmental effects through perturbation of estrogen receptor signalling. Whilst the exposure of humans to low levels of synthetic environmental estrogens is assumed to be hazardous, exposure to milligram per kilogram levels of phytoestrogens in foods and dietary supplements is frequently proposed to be life enhancing. Given this apparent paradox, an important question is whether estrogens derived from different sources induce their estrogenic effects through similar mechanisms. Comparative transcript profiling revealed that in the rodent uterus, a synthetic estrogen (diethylstilbestrol) and a phytoestrogen (genistein) operate via a molecular mechanism analogous to that of the physiological estrogen, E2.

These data define, at an unprecedented level of detail, the transcriptional mechanism by which ER ligands drive proliferation and differentiation in a reproductive organ.

Volume 9

24th Joint Meeting of the British Endocrine Societies

British Endocrine Societies 

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