ABSTRACT
Estrogens are normally produced in cyclic fashion in adult females and induce transient effects in reproductive organs, brain, and pituitary, allowing for cyclic reproductive activity. Epidemiological studies also link estrogens to cancers of the endometrium and breast. Ligand activation of the receptor leads to its interaction with a specific DNA sequence, the estrogen response element (ERE), in the promoter region of target genes. In addition to activation by ligand binding, estrogen receptors are also the targets of cellular kinases, which specifically phosphorylate the receptor on several serine or tyrosine sites. Most xeonestrogens have been shown to work through activation of estrogen receptor (ER), either ERα or ERß in a manner similar to natural ligands. Several observations suggest that E2 and some environmental estrogens act through mechanisms that either do not involve the ER or act on the receptor indirectly. In the ovaries, granulosa cells synthesize estrogens from androgens secreted by surrounding thecal cells.
