Estrogens bind to specific nuclear receptors in target cells and produce effects by regulating protein synthesis. Estrogen receptors (ERs) have been demonstrated in female sex organs, breast, pituitary, liver, bone, blood vessels, heart, CNS and in certain hormone responsive breast carcinoma cells.
MECHANISM OF ACTION
Estrogens bind to
specific nuclear receptors in target cells and produce effects by regulating
protein synthesis. Estrogen receptors (ERs) have been demonstrated in female sex
organs, breast, pituitary, liver, bone, blood vessels, heart, CNS and in
certain hormone responsive breast carcinoma cells. The ER is analogous to other
steroid receptors: agonist binding to the ligand binding domain brings about
receptor dimerization and interaction with ‘estrogen response elements’ (EREs)
of target genes. Gene transcription is promoted through certain coactivator proteins. On binding an estrogen antagonist the receptor assumes a different conformation and interacts with other
corepressor proteins inhibiting gene
transcription.
Two ERs designated ERα and ERβ have been identified,
cloned and structurally characterized. Most tissues express both subtypes but
ERα predominates in
uterus, vagina, breast, hypothalamus and blood vessels, while ERβ predominates in
prostate gland of males and ovaries in females. Estradiol binds to both ERα and ERβ with equal affinity,
but certain ligands may have differing affinities. More importantly ERα and ERβ may have a different
pattern of interaction with coactivators and corepressors.
Few nongenomic rapid
actions of estrogens in certain tissues mediated through the same ER have also
been observed.
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