Estrogen receptor transcription and transactivation Estrogen receptor knockout mice: what their phenotypes reveal about mechanisms of estrogen action

Natural, synthetic and environmental estrogens have numerous effects on the development and physiology of mammals. Estrogen is primarily known for its role in the development and functioning of the female reproductive system. However, roles for estrogen in male fertility, bone, the circulatory syste m and immune system have been established by clinical observations regardin g sex differences in pathologies, as well as observations following menopau se or castration. The primary mechanism of estrogen action is via binding a nd modulation of activity of the estrogen receptors (ERs), which are ligand -dependent nuclear transcription factors. ERs are found in highest levels i n female tissues critical to reproduction, including the ovaries, uterus, c ervix, mammary glands and pituitary gland. Since other affected tissues hav e extremely low levels of ER, indirect effects of estrogen, for example ind uction of pituitary hormones that affect the bone, have been proposed. The development of transgenic mouse models that lack either estrogen or ER have proven to be valuable tools in defining the mechanisms by which estrogen e xerts its effects in various systems. The aim of this article is to review the mouse models with disrupted estrogen signaling and describe the associa ted phenotypes.