Estrogen receptor alpha

Protein coding gene in the species Homo sapiens

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)

Phytoestrogens (e. g., coumestrol, daidzein, genistein, miroestrol)
Selective estrogen receptor modulators (e. g., tamoxifen, clomifene, raloxifene)

Antiestrogens (e. g., fulvestrant, ICI 164384, ethamoxytriphetol)

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.

ERα is essential in the maturation of the female reproductive phenotype. In the absence of ERα, the ERKO mouse develops an adult uterus, indicating that ERα may not mediate the initial growth of the uterus. Although classical studies have suggested that negative feedback effects of estrogen also operate through ERα, female mice lacking ERα in kisspeptin expressing neurons continue to demonstrate a degree of negative feedback response.

Estrogen insensitivity syndrome is a very rare condition characterized by a defective ERα that is insensitive to estrogens. The clinical presentation of a female was observed to include absence of breast development and other female secondary sexual characteristics at puberty, hypoplastic uterus, primary amenorrhea, enlarged multicystic ovaries and associated lower abdominal pain, mild hyperandrogenism (manifested as cystic acne), and delayed bone maturation as well as an increased rate of bone turnover. and dysmenorrhea. In patients with breast cancer, mutations in the gene encoding ERα (ESR1) have been associated with resistance to endocrine therapy, especially aromatase inhibitors.