Estrogen signaling pathway

Estrogens, also known as oestrogen, is steroid hormone and the primary female sex hormone. It is responsible for the regulation of growth, differentiation and function of the reproductive system and several other target tissues. There are three major endogenous estrogens in females that have estrogenic hormonal activity: estrone, estradiol, and estriol. The estrane steroid estradiol is the most potent and prevalent of these. Estrogens are synthesized in all vertebrates as well as some insects. The actions of estrogen are mediated by the estrogen receptor (ER), a dimeric nuclear protein that binds to DNA and controls gene expression. Estrogen mediates its cellular actions through two signaling pathways classified as "nuclear-initiated steroid signaling" and "membrane-initiated steroid signaling". In the "nuclear" pathway, estrogen binds either ERα or ERβ, which in turn translocates to the nucleus, binds DNA at ERE elements and activates the expression of ERE-dependent genes. In "membrane" pathway, Estrogen can exert its actions through a subpopulation of ER at the plasma membrane (mER) or novel G-protein coupled E2 receptors (GPER). Upon activation of these receptors various signaling pathways (i.e. Ca2+, cAMP, protein kinase cascades) are rapidly activated and ultimately influence downstream transcription factors. Estrogen signaling is often dysregulated in breast cancer and osteoporosis.

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