Estrogen receptor alpha (ERα), also known as NR3A1 (nuclear receptor subfamily 3, group A, member 1), is one of two main types of estrogen receptor, a nuclear receptor (mainly found as a chromatin-binding protein) that is activated by the sex hormone estrogen. In humans, ERα is encoded by the gene ESR1 (EStrogen Receptor 1). The estrogen receptor (ER) is a ligand-activated transcription factor composed of several domains important for hormone binding, DNA binding, and activation of transcription. Alternative splicing results in several ESR1 mRNA transcripts, which differ primarily in their 5-prime untranslated regions. The translated receptors show less variability. Endogenous estrogens (e.g., estradiol, estrone, estriol, estetrol) Natural estrogens (e.g., conjugated equine estrogens) Synthetic estrogens (e.g., ethinylestradiol, diethylstilbestrol) Agonists of ERα selective over ERβ include: Propylpyrazoletriol (PPT) 16α-LE2 (Cpd1471) 16α-IE2 ERA-63 (ORG-37663) SKF-82,958 – also a D1-like receptor full agonist (R,R)-Tetrahydrochrysene ((R,R)-THC) – actually not selective over ERβ, but rather an antagonist instead of an agonist of ERβ Phytoestrogens (e.g., coumestrol, daidzein, genistein, miroestrol) Selective estrogen receptor modulators (e.g., tamoxifen, clomifene, raloxifene) Antiestrogens (e.g., fulvestrant, ICI-164384, ethamoxytriphetol) Antagonists of ERα selective over ERβ include: Methylpiperidinopyrazole (MPP) ERα plays a role in the physiological development and function of a variety of organ systems to varying degrees, including the reproductive, central nervous, skeletal, and cardiovascular systems. Accordingly, ERα is widely expressed throughout the body, including the uterus and ovary, male reproductive organs, mammary gland, bone, heart, hypothalamus, pituitary gland, liver, lung, kidney, spleen, and adipose tissue. The development and function of these tissues is disrupted in animal models lacking active ERα genes, such as the ERα knockout mouse (ERKO), providing a preliminary understanding of ERα function at specific target organs.

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