The glucocorticoid receptor inhibits the human prolactin gene expression by interference with Pit-1 activity.
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.
Nalda
A M
AM
Laboratoire de Biologie Moléculaire et de Génie Génétique, Institut de Chimie-B6, Université de Liège, Belgium.
Martial
J A
JA
Muller
M
M
D000818:Animals; D019556:COS Cells; D000242:Cyclic AMP / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D011388:Prolactin / Q000037:antagonists & inhibitors* / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011485:Protein Binding / Q000235:genetics; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000502:physiology*; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C494187:POU1F1 protein, human; C494186:Pou1f1 protein, rat; D011965:Receptors, Glucocorticoid; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; D011388:Prolactin; D004247:DNA; D000242:Cyclic AMP