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

Molecular and Cellular Endocrinology
A M NaldaM Muller

Abstract

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.

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Citations

Dec 15, 2006·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·R BadrinarayananK Balasubramanian
Nov 29, 2005·Molecular and Cellular Endocrinology·Kathleen Van CraenenbroeckGuy Haegeman
Feb 3, 2012·Physiological Reviews·Carolina Perez-CastroEduardo Arzt

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