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Article Abstract
The widely used rat uterotrophic assay to assess known and potential estrogenic compounds only considers uterine weight gain as endpoint measurement. To complement this method with an advanced technology that reveals molecular targets, we analyzed changes in protein expression using label-free quantitative proteomics by nanoflow liquid chromatography coupled with high-resolution mass spectrometry and tandem mass spectrometry from uterine protein extracts of ovariectomized rats after daily 17β-estradiol exposure for five days in comparison with those of vehicle-treated control animals. Our discovery-driven study revealed 165 uterine proteins significantly regulated by estrogen treatment and mapped by pathway analyses. Estrogen-regulated proteins represented cell death, survival and development, cellular growth and proliferation, and protein synthesis as top molecular and cellular functions, and a network found with the presence of nuclear estrogen receptor(s) as a prominent molecular node confirmed the relevance of our findings to hormone-associated events. An exploratory application of targeted proteomics to bisphenol A as a well-known example of an estrogenic endocrine disruptor is also presented. Overall, the results of this study have demonstrated the power of combining untargeted and targeted quantitative proteomic strategies to identify and verify candidate molecular markers for the evaluation of endocrine-disrupting chemicals to complement a conventional bioassay.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914934 | PMC |
| http://dx.doi.org/10.3390/ijms22041686 | DOI Listing |
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Article Synopsis
- Prolame, a synthetic estrogen, shows promise as a safer alternative by providing antidepressant and anxiolytic effects in ovariectomized young adult rats, but its efficacy in simulating menopause conditions in older rats is unclear.
- In a study, prolame and traditional estrogen were administered to middle-aged female rats, revealing that prolame retained its beneficial effects in ovariectomized rats while traditional estrogen's effects were not observed in intact middle-aged rats, suggesting prolame could be a favorable EHRT option with fewer side effects.