Estrogen signaling pathway

What Is Estrogen?

Estrogens, also known as oestrogen, is steroid hormone and the primary female sex hormone. It plays an important role in the maintenance of female secondary characteristics, the occurrence and development of breast cancer, gastric cancer and cardiovascular diseases.

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.

Estrogen Signaling Pathway

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 binds to ER to regulate gene transcription in the nucleus or activate kinases in the cytoplasm.

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 and Disease

Estrogen plays an important role in the reproductive system and other tissues such as bone tissue and the cardiovascular system. Many pathological conditions are related to the production of estrogen, such as osteoporosis and breast cancer, which are related to estrogen. Estrogen inhibitors are commonly used to treat hormone-dependent breast cancer and occasionally prostate cancer. Estrogen also has important effects on the immune system.