Distinct effects on the conformation of estrogen receptor α and β by both the antiestrogens ICI 164,384 and ICI 182,780 leading to opposite effects on receptor stability

Gert Jan C.M. Van Den Bemd, George G.J.M. Kuiper, Huibert A.P. Pols, Johannes P.T.M. Van Leeuwen

Research output: Contribution to journalArticleAcademicpeer-review

54 Citations (Scopus)
42 Downloads (Pure)

Abstract

Tissue-specific effects of 17β-estradiol (E2) and synthetic estrogen receptor (ER) ligands on target gene regulation might, at least partly, be explained by a selective ligand-induced conformational change of their receptors (ERα and ERβ). In this study, the effects of E2 and the synthetic ER ligands tamoxifen (TAM), ICI 164,384, and ICI 182,780 on the conformation of ERα and ERβ were examined using limited proteolytic digestion analysis. We found that E2 induced a conformational change of ERα resulting in the protection of a 30-kDa product, whereas TAM protected a 28-kDa fragment. Strikingly, the ERα conformational change induced by both ICI 164,384 and ICI 182,780 did not result in protection but rather seems to induce a ligand concentration-dependent increase in proteolytic degradation of the 30- and 28-kDa products. Incubation of ERβ with E2 resulted in an increased protection of a 30-kDa fragment, whereas with TAM protection of a 29-kDa fragment was observed. In contrast to the situation with ERα, ICI 164,384 and ICI 182,780 incubation induced the protection in a manner similar to 30-kDa fragment E2. In addition, the ICI compounds also induced in a dose-dependent manner the preservation of a 32-kDa fragment. Our observations demonstrate that ICI 164,384 and ICI 182,780 have distinct effects on the conformation of ERα and ERβ, resulting in receptor subtype-selective opposite effects on receptor stability in vitro.

Original languageEnglish
Pages (from-to)1-5
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume261
Issue number1
DOIs
Publication statusPublished - 22 Jul 1999

Fingerprint

Dive into the research topics of 'Distinct effects on the conformation of estrogen receptor α and β by both the antiestrogens ICI 164,384 and ICI 182,780 leading to opposite effects on receptor stability'. Together they form a unique fingerprint.

Cite this