Regulation of specific target genes and biological responses by estrogen receptor subtype agonists.
Estrogenic effects are mediated through two estrogen receptor (ER) subtypes, ERα and ERβ. Estrogens are the most commonly prescribed drugs to treat menopausal conditions, but by non-selectively triggering both ERα and ERβ pathways in different tissues they can cause serious adverse effects. The different sizes of the binding pockets and sequences of their activation function domains indicate that ERα and ERβ should have different specificities for ligands and biological responses that can be exploited for designing safer and more selective estrogens. ERα and ERβ regulate different genes by binding to different regulatory elements and recruiting different transcription and chromatin remodeling factors that are expressed in a cell-specific manner. ERα-selective and ERβ-selective agonists have been identified that demonstrate that the two ERs produce distinct biological effects. ERα and ERβ agonists are a promising new approach for treating specific conditions associated with menopause.
Leitman
Dale C
DC
Department of Nutritional Science and Toxicology, University of California, Berkeley, CA, USA. dale@leitmanlab.com
Paruthiyil
Sreenivasan
S
Vivar
Omar I
OI
Saunier
Elise F
EF
Herber
Candice B
CB
Cohen
Isaac
I
Tagliaferri
Mary
M
Speed
Terence P
TP
D001943:Breast Neoplasms / Q000378:metabolism / Q000517:prevention & control*; D002460:Cell Line; D042002:Chromatin Assembly and Disassembly; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D053263:Gene Regulatory Networks; D019584:Hot Flashes / Q000188:drug therapy; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D008024:Ligands; D008593:Menopause; D058990:Molecular Targeted Therapy; D056918:Nuclear Receptor Coactivators / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D020845:Selective Estrogen Receptor Modulators / Q000378:metabolism / Q000494:pharmacology*; D014157:Transcription Factors / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D008024:Ligands; D056918:Nuclear Receptor Coactivators; D020845:Selective Estrogen Receptor Modulators; D014157:Transcription Factors; D004958:Estradiol