multiple routes to oestrogen antagonism多个航线雌激素拮抗.pdfVIP

Pharmaceuticals 2010, 3, 3417-3434; doi:10.3390/ph3113417 OPEN ACCESS pharmaceuticals ISSN 1424-8247 /journal/pharmaceuticals Article Multiple Routes to Oestrogen Antagonism Hilary R. Glover, Stewart Barker, Sylvanie D. M. Malouitre, John R. Puddefoot and Gavin P. Vinson * School of Biological and Chemical Sciences, Queen Mary, University of London, E1 4NS, UK * Author to whom correspondence should be addressed; E-Mail: G.P.Vinson@qmul.ac.uk; Tel.: +44-207-982-6330. Received: 26 September 2010; in revised form: 19 October 2010/ Accepted: 25 October 2010 / Published: 29 October 2010 Abstract: Several lines of evidence attest to the existence of alternative ligand binding sites on the oestrogen receptor (ER), including non-competitive inhibition by trilostane or tamoxifen. It is possible that the inhibitory action of conventional oestrogen agonists at high concentrations may indicate that they too interact at alternative ER sites, albeit at low affinity. To test this possibility an oestrogen reporter assay was used to compare the activity of different oestrogens and antagonists in breast cancer and prostate cell lines. All four cell lines tested contained different amounts of oestrogen receptor α (ERα), ERβ, progesterone receptor and coregulator mRNA. Though differences were observed in response to stimulation and inhibition, these correlated only with the presence or absence of ERα, and not with the other