A report on Estrogen receptor and Estrogen receptor beta

A dimer of the ligand-binding region of ERβ (PDB rendering based on ).

The domain structures of ERα and ERβ, including some of the known phosphorylation sites involved in ligand-independent regulation.

A dimer of the ligand-binding region of ERα (PDB rendering based on ).

Estrogen receptor beta (ERβ) also known as NR3A2 (nuclear receptor subfamily 3, group A, member 2) is one of two main types of estrogen receptor—a nuclear receptor which is activated by the sex hormone estrogen.

- Estrogen receptor beta

Two classes of ER exist: nuclear estrogen receptors (ERα and ERβ), which are members of the nuclear receptor family of intracellular receptors, and membrane estrogen receptors (mERs) (GPER (GPR30), ER-X, and Gq-mER), which are mostly G protein-coupled receptors.

- Estrogen receptor

13 related topics with Alpha

Estrogen receptor alpha

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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 that is activated by the sex hormone estrogen.

Agonists of ERα selective over ERβ include:

Tamoxifen, a nonsteroidal triphenylethylene antiestrogen and a widely used drug in the treatment of breast cancer.

Selective estrogen receptor modulator

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Figure 2: Nolvadex (tamoxifen) 20-milligram tablets (UK)

Figure 3: The domain structures of ERα and ERβ, including some of the known phosphorylation sites involved in ligand-independent regulation.

Figure 4: Structural basis for the mechanism of estrogen receptor agonist and antagonist action. The structures shown here are of the ligand binding domain (LBD) of the estrogen receptor (green cartoon diagram) complexed with either the agonist diethylstilbestrol (top, ) or antagonist 4-hydroxytamoxifen (bottom, ). The ligands are depicted as space filling spheres (white = carbon, red = oxygen). When an agonist is bound to a nuclear receptor, the C-terminal alpha helix of the LBD (H12; light blue) is positioned such that a coactivator protein (red) can bind to the surface of the LBD. Shown here is just a small part of the coactivator protein, the so-called NR box containing the LXXLL amino acid sequence motif. Antagonists occupy the same ligand binding cavity of the nuclear receptor. However antagonist ligands in addition have a sidechain extension which sterically displaces H12 to occupy roughly the same position in space as coactivators bind. Hence coactivator binding to the LBD is blocked.

Figure 5: 4-hydroxytamoxifen (red) overlaid with 17β-estradiol (black)

Figure 6: Trans-form of clomifene with the triphenylethylene structure in red.

Figure 8: Chemical structure of toremifene

Figure 9: Raloxifene has a benzothiophene group (red) and is connected with a flexible carbonyl hinge to a phenyl 4-piperidinoethoxy side chain (green).

Figure 10: Chemical structure of nafoxidine with the dihydronapthalene group in red.

Figure 11: Chemical structure of lasofoxifene shows cis-oriented phenyls.

Figure 12: Bazedoxifene includes an indole system (red) which is connected to an amine through a benzyloxyethyl chain (green).

Figure 13: Chemical structure of ospemifene. Ethoxy side chain ends with a hydroxy group (red) instead of a dimethylamino group as with first-generation SERMs.

Figure 14: The ABCD steroid ring system in 17β-estradiol.

Figure 15: "A ring" (A) and "D ring" (D) marked in raloxifene.

Selective estrogen receptor modulators (SERMs), also known as estrogen receptor agonist/antagonists (ERAAs), are a class of drugs that act on the estrogen receptor (ER).

Two different subtypes of ER have been identified, ERα and ERβ.

Tamoxifen

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Selective estrogen receptor modulator used to prevent breast cancer in women and treat breast cancer in women and men.

Crystallographic structure of afimoxifene (carbon = white, oxygen = red, nitrogen = blue) complexed with ligand binding domain of estrogen receptor alpha (ERα) (cyan ribbon).

Tamoxifen is used for the treatment of both early and advanced estrogen receptor-positive (ER-positive or ER+) breast cancer in pre- and postmenopausal women.

Per one study, tamoxifen had 7% and 6% of the affinity of estradiol for the ERα and ERβ, respectively, whereas afimoxifene had 178% and 338% of the affinity of estradiol for the ERα and ERβ, respectively.

Diethylstilbestrol

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Nonsteroidal estrogen medication, which is presently rarely used.

Testosterone levels with no treatment and with various estrogens in men with prostate cancer. Determinations were made with an early radioimmunoassay (RIA). Source was Shearer et al. (1973).

Testosterone levels with placebo and 0.2 to 5 mg/day diethylstilbestrol (DES) for 6 months in men with prostate cancer. Determinations were made with a radioimmunoassay (RIA). Source was Kent et al. (1973).

Chemical structures of estradiol and DES. Note the preservation of the two hydroxyl groups in DES and the similar distance between them relative to estradiol, which is notable when it is considered that DES was discovered serendipitously.

DES is an estrogen, or an agonist of the estrogen receptors, the biological target of estrogens like estradiol.

It has approximately 468% and 295% of the affinity of estradiol at the ERα and ERβ, respectively.

Estradiol

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Estrogen steroid hormone and the major female sex hormone.

Estradiol levels across the menstrual cycle in 36 normally cycling, ovulatory women, based on 956 specimens. The horizontal dashed lines are the mean integrated levels for each curve. The vertical dashed line in the center is mid-cycle.

The estrogen receptor, as well as the progesterone receptor, have been detected in the skin, including in keratinocytes and fibroblasts.

Estradiol affects target tissues mainly by interacting with two nuclear receptors called estrogen receptor α (ERα) and estrogen receptor β (ERβ).

Estriol

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Steroid, a weak estrogen, and a minor female sex hormone.

Estriol is an estrogen, specifically an agonist of the estrogen receptors ERα and ERβ.

Raloxifene

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Medication used to prevent and treat osteoporosis in postmenopausal women and those on glucocorticoids.

Raloxifene is a selective estrogen receptor modulator (SERM) and therefore a mixed agonist–antagonist of the estrogen receptor (ER).

Relative to estradiol, raloxifene has been reported to possess about 8 to 34% of the affinity for the ERα and 0.5 to 76% of the affinity for the ERβ.

Estrone

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Steroid, a weak estrogen, and a minor female sex hormone.

Estrone is an estrogen, specifically an agonist of the estrogen receptors ERα and ERβ.

Antiestrogen

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Antiestrogens, also known as estrogen antagonists or estrogen blockers, are a class of drugs which prevent estrogens like estradiol from mediating their biological effects in the body.

They act by blocking the estrogen receptor (ER) and/or inhibiting or suppressing estrogen production.

Antiestrogens act as antagonists of the estrogen receptors, ERα and ERβ.

Genistein

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Naturally occurring compound that structurally belongs to a class of compounds known as isoflavones.

Besides functioning as an antioxidant and anthelmintic, many isoflavones have been shown to interact with animal and human estrogen receptors, causing effects in the body similar to those caused by the hormone estrogen.

full agonist of ERβ (EC50 = 7.62 nM) and, to a much lesser extent (~20-fold), full agonist or partial agonist of ERα