The effects of estrogen are primarily mediated via estrogen receptor-α, which stimulates target gene transcription through two activation functions, AF-1 in the N-terminal and AF-2 in the ligand binding domain. These authors analyzed mouse models lacking the entire ERα protein, ERα AF-1, or ERα AF-2. They found that ERα AF-2 was required for the estrogenic effects on all parameters evaluated, whereas the role of ERα AF-1 is tissue-specific, with a crucial role in trabecular bone and uterus but not cortical bone.
Börjesson AE, Windahl SH, Lagerquist MK, Engdahl C, Frenkel B, Movérare-Skrtic S, et al
Proc Natl Acad Sci U S A. 2011 Apr 12;108(15):6288-93. Epub 2011 Mar 28.