Estrogen & Estrogen Receptor

Target tissues of estrogen in females & males “Good” estrogen actions “Bad” estrogen actions Maintain bone Promoter proliferation of Maintain sexual function Cardiovascular protection Mammary epithelium Protect brain function Endometrial epithelium

Estrogen receptor (ER) signaling pathways NEJM 2006;354:270-82 Ovarian steroid hormone

Effects of ER on different cell types

Estrogen receptor and Breast cancer

Role of E2/ER in breast carcinogenesis Initiators Promoters ER positive

Functional domains & expression of human ERs Phosphorylation Acetylation cys447 Palmitoylation Expression breast, uterus, and bone ovary, prostate, testis, lung, thymus, spleen, and brain

Regulation of ER activity by multiple coregulators

Chromatin modification in ER-mediated transcription

Transcriptional regulation modes of nuclear receptors