title: Estrogen receptors: how do they signal and what are their targets.
abstract: During the past decade there has been a substantial advance in our understanding of estrogen signaling both from a clinical as well as a preclinical perspective. Estrogen signaling is a balance between two opposing forces in the form of two distinct receptors (ER alpha and ER beta) and their splice variants. The prospect that these two pathways can be selectively stimulated or inhibited with subtype-selective drugs constitutes new and promising therapeutic opportunities in clinical areas as diverse as hormone replacement, autoimmune diseases, prostate and breast cancer, and depression. Molecular biological, biochemical, and structural studies have generated information which is invaluable for the development of more selective and effective ER ligands. We have also become aware that ERs do not function by themselves but require a number of coregulatory proteins whose cell-specific expression explains some of the distinct cellular actions of estrogen. Estrogen is an important morphogen, and many of its proliferative effects on the epithelial compartment of glands are mediated by growth factors secreted from the stromal compartment. Thus understanding the cross-talk between growth factor and estrogen signaling is essential for understanding both normal and malignant growth. In this review we focus on several of the interesting recent discoveries concerning estrogen receptors, on estrogen as a morphogen, and on the molecular mechanisms of anti-estrogen signaling.
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
authors.forename: Nina
authors.initials: N
authors.lastname: Heldring
authors.forename: Ashley
authors.initials: A
authors.lastname: Pike
authors.forename: Sandra
authors.initials: S
authors.lastname: Andersson
authors.forename: Jason
authors.initials: J
authors.lastname: Matthews
authors.forename: Guojun
authors.initials: G
authors.lastname: Cheng
authors.forename: Johan
authors.initials: J
authors.lastname: Hartman
authors.forename: Michel
authors.initials: M
authors.lastname: Tujague
authors.forename: Anders
authors.initials: A
authors.lastname: Ström
authors.forename: Eckardt
authors.initials: E
authors.lastname: Treuter
authors.forename: Margaret
authors.initials: M
authors.lastname: Warner
authors.forename: Jan-Ake
authors.initials: JA
authors.lastname: Gustafsson
mesh_terms: D000818:Animals; D004967:Estrogens / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D006801:Humans; D020033:Protein Isoforms; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D004967:Estrogens; D020033:Protein Isoforms; D011960:Receptors, Estrogen