Selective estrogen receptor modulators

Selective estrogen receptor modulators, SERMs, form a heterogeneous class of non-steroidal substances that act not only as estrogens but also as antiestrogens.

After binding to the estrogen receptors -ERalpha + ERbeta-, "selective estrogen receptor modulators" initiate a ligand-specific conformational change of both receptors, which determines the type of interaction with DNA and with certain regulatory proteins.

In the inactive state, the estrogen receptors -ERalpha + ERbeta- are located in the cytoplasm of cells and bound to so-called heat shock proteins such as HSP90. When estrogens bind to the estrogen receptor, the heat shock protein is released.

In a next step, a translocation of the hormone receptor complex into the cell nucleus takes place. There the hormone receptor complexes can bind to so-called "estrogen-responsive elements" of the DNA in the form of dimers. By recruiting further coactivators or core compressors, the gene expression of target genes can then be activated or inhibited (see figure)

The quality and quantity of the coregulatory proteins in the cell are thus decisive for an agonistic or antagonistic effect of the estrogen receptor on target gene expression.

The exact profile of the SERM depends on its chemical structure: tamoxifen is antagonistic in breast tissue and agonistic in utero.

Vasomotor symptoms, thrombosis, venous thromboembolism and the estrogen-agonistic increase in the risk of endometrial carcinoma. Also: fatigue, disinterest, hot flushes, slight loss of hair, nausea, constipation, dizziness, dry mucous membranes, rash, itching. Arthralgia, myalgia.

Representatives of this group are:

• Tamoxifen
• Toremifene (metastasized breast carcinoma)
• Fulvestrant (advanced or metastasized breast carcinoma)