Home LiteratureArticle Details
PMID: 6327286 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

DNA binding properties of glucocorticosteroid receptors bound to the steroid antagonist RU-486.

The EMBO journal ·Vol. 3 ·No. 4 ·1984-04-00 ·Pages 751-5

Bourgeois S, Pfahl M, Baulieu EE

Abstract

RU-486 is an anti-fertility steroid which also has anti-glucocorticosteroid effects. RU-486 is shown to be a strong antagonist of the glucocorticosteroid-induced cytolytic response of the murine thymoma lines W7TB and T1M1b , and of the induction of mouse mammary tumor virus (MMTV) mRNA in T1M1b cells. The glucocorticosteroid receptor of W7 cells has high affinity for RU-486 (Kd = 3 X 10(-9) M) but the complex formed has low nuclear transfer capacity. Binding of RU-486, as compared with the glucocorticosteroid agonist triamcinolone acetonide, to mouse receptor results in a decreased affinity for DNA in general and a reduced specific recognition of a site in the promoter region of MMTV proviral DNA. The RU-486 complex formed with rat liver receptor exhibits the same behavior; in addition, it is shown that only a fraction of these complexes are activated by temperature and these form highly salt-sensitive interactions with DNA. These results indicate that the binding of RU-486 to glucocorticosteroid receptors mimics pharmacologically the properties of a class of receptor variants (nt-) which are non-functional and have reduced nuclear transfer and altered DNA binding capacity. These results substantiate the importance of DNA binding in receptor function.

MeSH Terms
Animals Cell Line DNA/metabolism DNA, Viral/metabolism Dexamethasone/metabolism Estrenes/metabolism,pharmacology Glucocorticoids/antagonists & inhibitors Mammary Tumor Virus, Mouse/genetics Mice Mice, Inbred BALB C Mifepristone RNA, Messenger/biosynthesis RNA, Viral/biosynthesis Receptors, Glucocorticoid/metabolism Receptors, Steroid/metabolism Thymoma/metabolism Transcription, Genetic/drug effects
Chemicals
DNA, Viral Estrenes Glucocorticoids RNA, Messenger RNA, Viral Receptors, Glucocorticoid Receptors, Steroid Mifepristone Dexamethasone DNA
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Bourgeois S
Pfahl M
Baulieu E E
References (26)
26 references, click to expand
  1. Glucocorticoid receptors: relations between steroid binding and biological effects.
    J Mol Biol. 1972 Jun 14;67(1):99-115 PMID: 4402888
  2. Correlation of glucocorticoid receptor binding sites on MMTV proviral DNA with hormone inducible transcription.
    Science. 1983 Dec 23;222(4630):1341-3 PMID: 6318311
  3. Repressors.
    Adv Protein Chem. 1976;30:1-99 PMID: 779429
  4. Diploid and haploid states of the glucocorticoid receptor gene of mouse lymphoid cell lines.
    Cell. 1977 Jun;11(2):423-30 PMID: 560913
  5. Interaction of glucocorticoid receptors from lymphoid cell lines with their nuclear acceptor sites.
    Mol Cell Endocrinol. 1978 Apr;10(2):175-91 PMID: 26620
  6. General features of steroid resistance on lymphoid cell lines.
    Mol Cell Endocrinol. 1978 Apr;10(2):193-207 PMID: 566227
  7. Purification of the glucocorticoid receptor from rat liver cytosol.
    J Biol Chem. 1979 Sep 25;254(18):9284-90 PMID: 479195
  8. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease.
    Biochemistry. 1979 Nov 27;18(24):5294-9 PMID: 518835
  9. 'Activation-labile' glucocorticoid-receptor complexes of a steroid-resistant variant of CEM-C7 human lymphoid cells.
    Nature. 1980 Jul 31;286(5772):507-10 PMID: 6967568
  10. Three-step purification of glucocorticoid receptors from rat liver.
    Eur J Biochem. 1980;108(1):47-53 PMID: 7408853
  11. Hormone-responsive expression of an endogenous proviral gene of mouse mammary tumor virus after molecular cloning and gene transfer into cultured cells.
    Proc Natl Acad Sci U S A. 1981 Apr;78(4):2038-42 PMID: 6264458
  12. Purified glucocorticoid receptors bind selectively in vitro to a cloned DNA fragment whose transcription is regulated by glucocorticoids in vivo.
    Proc Natl Acad Sci U S A. 1981 Nov;78(11):6628-32 PMID: 6273877
  13. Characterization of a new type of thymoma variants supersensitive to dexamethasone.
    J Steroid Biochem. 1981 Dec;15:25-34 PMID: 7339252
  14. Chicken oviduct progesterone receptor: location of specific regions of high-affinity binding in cloned DNA fragments of hormone-responsive genes.
    Cell. 1982 Mar;28(3):621-32 PMID: 6280879
  15. Selective binding of chicken progesterone receptor A subunit to a DNA fragment containing ovalbumin gene sequences.
    Biochem Biophys Res Commun. 1982 Mar 15;105(1):96-104 PMID: 7092862
  16. Immunochemical analysis of the glucocorticoid receptor: identification of a third domain separate from the steroid-binding and DNA-binding domains.
    Proc Natl Acad Sci U S A. 1982 Jul;79(14):4260-4 PMID: 6181503
  17. Oestrogen and progesterone receptors in chick oviduct chromatin after administration of oestradiol, progesterone or anti-oestrogen.
    Biochem J. 1982 Jun 15;204(3):653-62 PMID: 7126160
  18. Purified glucocorticoid receptor-hormone complex from rat liver cytosol binds specifically to cloned mouse mammary tumor virus long terminal repeats in vitro.
    Proc Natl Acad Sci U S A. 1982 Sep;79(17):5157-61 PMID: 6291027
  19. [The effects of an antiprogesterone steroid in women: interruption of the menstrual cycle and of early pregnancy].
    C R Seances Acad Sci III. 1982 May 17;294(18):933-8 PMID: 6814714
  20. Dramatic growth of mice that develop from eggs microinjected with metallothionein-growth hormone fusion genes.
    Nature. 1982 Dec 16;300(5893):611-5 PMID: 6958982
  21. Multiple specific binding sites for purified glucocorticoid receptors on mammary tumor virus DNA.
    J Cell Biochem. 1982;19(3):241-7 PMID: 6296168
  22. Demethylation and expression of murine mammary tumor proviruses in mouse thymoma cell lines.
    Proc Natl Acad Sci U S A. 1983 Jan;80(1):110-4 PMID: 6296860
  23. Specific binding of the glucocorticoid-receptor complex to the mouse mammary tumor proviral promoter region.
    Cell. 1982 Dec;31(2 Pt 1):475-82 PMID: 6297768
  24. Transcription initiation of transfected mouse mammary tumor virus LTR DNA is regulated by glucocorticoid hormones.
    Nucleic Acids Res. 1983 Jul 25;11(14):4713-25 PMID: 6308557
  25. The glucocorticoid receptor binds to defined nucleotide sequences near the promoter of mouse mammary tumour virus.
    Nature. 1983 Aug 25-31;304(5928):749-52 PMID: 6310405
  26. Steroid hormone receptors.
    Vitam Horm. 1975;33:649-736 PMID: 180682
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1984-04-00
Pages
751-5
Language
English
Region
England
NLM ID
8208664
PMCID
PMC557421
Subset
IM
Grants
NCI NIH HHS · CA36146 · United States
NIGMS NIH HHS · GM20868 · United States
External Links
PubMed source PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2