Estrogen produces a variety of physiological functions in numerous tissues in both females and males. The actions can occur through cytoplasmic and nuclear activities of two receptor protein isoforms, ERα and ERβ, and multiple cell signaling mechanisms, including non-genomic and genomic actions. Genomic actions involve either direct DNA binding or tethered gene regulation. We describe herein some of the physiological responses of estrogen occurring through a particular receptor by way of gene targeting experimental models. We describe additional experimental models that isolate specific estrogen receptor activities to determine and evaluate the physiological responses, in reproductive/gonadal tissues, neuroendocrine actions, and obesity related to adipose tissue and bone as some examples, linked to that receptors’ functional domains and tissue specificity.
