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Receptor density dictates the behavior of a subset of steroid ligands in glucocorticoid receptor-mediated transrepression.

Abstract：

:By co-expressing glucocorticoid receptor (GR) and transcriptional reporter systems in GR-deficient Cos-7 cells, we profiled potency and efficacy of a panel of GR ligands as a function of GR expression levels (density). Our results show that potency and efficacy for GR full agonists, such as dexamethasone, in these transrepression assays are affected by receptor density. Intriguingly, receptor density dramatically influenced the behavior of the GR antagonist RU486 or the GR agonist medroxyprogesterone acetate (MPA). At high receptor density, both MPA and RU486 behaved as full agonists in transrepression: reducing GR density, however, resulted in conversion of these ligands from full agonist to full antagonists. In contrast, varying GR density could not convert cortisol and budesonide from GR agonists to antagonists. These results have clearly demonstrated, for the first time, an effect of receptor density on the agonist and antagonist properties of RU486 and MPA in GR-mediated transrepression.

journal_name

Int Immunopharmacol

journal_title

International immunopharmacology

authors

Zhao Q,Pang J,Favata MF,Trzaskos JM

doi

10.1016/j.intimp.2003.08.005

keywords:

subject

Has Abstract

pub_date

2003-12-01 00:00:00

pages

1803-17

issue

13-14

eissn

1567-5769

issn

1878-1705

pii

S1567-5769(03)00222-4

journal_volume

3

pub_type

杂志文章

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