Differential Ligand Activation of Estrogen Receptors ERα and ERβ at AP1 Sites

TLDR

The study examined how ERα and ERβ transactivate in response to various ligands at estrogen response and AP1 sites. At AP1 sites, estradiol activates transcription via ERα but represses it via ERβ, while antiestrogens such as tamoxifen, raloxifene, and ICI 164384 activate ERβ, indicating that ERα and ERβ elicit opposite transcriptional responses depending on ligand and response element.

Abstract

The transactivation properties of the two estrogen receptors, ERα and ERβ, were examined with different ligands in the context of an estrogen response element and an AP1 element. ERα and ERβ were shown to signal in opposite ways when complexed with the natural hormone estradiol from an AP1 site: with ERα, 17β-estradiol activated transcription, whereas with ERβ, 17β-estradiol inhibited transcription. Moreover, the antiestrogens tamoxifen, raloxifene, and Imperial Chemical Industries 164384 were potent transcriptional activators with ERβ at an AP1 site. Thus, the two ERs signal in different ways depending on ligand and response element. This suggests that ERα and ERβ may play different roles in gene regulation.