Estrogen receptors: how do they signal and what are their targets.
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.
Heldring
Nina
N
Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
Pike
Ashley
A
Andersson
Sandra
S
Matthews
Jason
J
Cheng
Guojun
G
Hartman
Johan
J
Tujague
Michel
M
Ström
Anders
A
Treuter
Eckardt
E
Warner
Margaret
M
Gustafsson
Jan-Ake
JA
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
D004967:Estrogens; D020033:Protein Isoforms; D011960:Receptors, Estrogen