期刊
BIOCHEMIA MEDICA
卷 24, 期 3, 页码 329-342出版社
CROATIAN SOC MEDICAL BIOCHEMISTS
DOI: 10.11613/BM.2014.035
关键词
estrogen signaling; extragonadal synthesis; epigenetic mechanisms; miRNA; DNA methylation
资金
- Slovenian Research Agency [ARMR19, P3-0298, J3-2330, J3-5511]
Estrogens have long been known as important regulators of the female reproductive functions; however, our understanding of the role estrogens play in the human body has changed significantly over the past years. It is now commonly accepted that estrogens and androgens have important functions in both female and male physiology and pathology. This is in part due to the local synthesis and action of estrogens that broadens the role of estrogen signaling beyond that of the endocrine system. Furthermore, there are several different mechanisms through which the three estrogen receptors (ERs), ER alpha, ER beta and G protein-coupled estrogen receptor 1 (GPER1) are able to regulate target gene transcription. ER alpha and ER beta are mostly associated with the direct and indirect genonnic signaling pathways that result in target gene expression. Membrane-bound GPER1 is on the other hand responsible for the rapid non-genonnic actions of estrogens that activate various protein-kinase cascades. Estrogen signaling is also tightly connected with another important regulatory entity, i.e. epigenetic mechanisms. Posttranslational histone modifications, microRNAs (miRNAs) and DNA methylation have been shown to influence gene expression of ERs as well as being regulated by estrogen signaling. Moreover, several coregulators of estrogen signaling also exhibit chromatin-modifying activities further underlining the importance of epigenetic mechanisms in estrogen signaling. This review wishes to highlight the newer aspects of estrogen signaling that exceed its classical endocrine regulatory role, especially emphasizing its tight intertwinement with epigenetic mechanisms.
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