The glucocorticoid receptor inhibits the human prolactin gene expression by interference with Pit-1 activity

Animals; COS Cells; Cyclic AMP/metabolism; DNA/metabolism; DNA-Binding Proteins/drug effects/*metabolism/physiology; *Gene Expression Regulation/drug effects; Hela Cells; Humans; Prolactin/*antagonists & inhibitors/*genetics; Promoter Regions, Genetic/drug effects; Protein Binding/genetics; Rats; Receptors, Glucocorticoid/*physiology; Transcription Factor Pit-1; Transcription Factors/drug effects/*metabolism/physiology; Tumor Cells, Cultured

Abstract :

[en] Glucocorticoids have been shown to inhibit the activity of the human prolactin (hPRL) promoter. Using transient expression experiments in rat pituitary cells, we located the sequence conferring glucocorticoid inhibition to a region which contains Pit-1 binding sites, responsible for pituitary-specific expression, but does not seem to contain a glucocorticoid receptor (GR) binding site. Co-transfection experiments in non-pituitary cell lines, using expression vectors for Pit-1 and different mutants of the human GR show that inhibition of the hPRL gene is seen only in the presence of Pit-1 and GR, and that the DNA binding function of the receptor is not required. Immunoprecipitation studies show that either anti-GR or anti-Pit-1 antibodies are able to co-precipitate GR and Pit-1, suggesting an interaction between these factors. We conclude that the activated GR functionally interferes with the pituitary specific factor Pit-1, thereby leading to the observed transcriptional repression.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Nalda, Asunción M; Université Paris XI

Martial, Joseph ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire

Muller, Marc ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire

Language :

English

Title :

The glucocorticoid receptor inhibits the human prolactin gene expression by interference with Pit-1 activity

Publication date :

1997

Journal title :

Molecular and Cellular Endocrinology

ISSN :

0303-7207

eISSN :

1872-8057

Publisher :

North Holland Publishing Company, Amsterdam, Netherlands

Volume :

134

Issue :

Pages :

129-37

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T3G-3RM6VK0-6&_user=532038&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000026659&_version=1&_urlVersion=0&_userid=532038&md5=821bf23156aa046426e8ee41a0fbd8e7#fn1

Commentary :

www.elsevier.com

Available on ORBi :

since 04 December 2009

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