Glucocorticoid repression of pro-opiomelanocortin gene transcription.

Transcription of the pro-opiomelanocortin (POMC) gene is repressed by glucocorticoids in the anterior pituitary gland. We have defined an element within the POMC promoter which is responsible for this regulatory feedback. This element, the "negative glucocorticoid response element" (nGRE), was localized in the proximal region of the POMC promoter and it contains a binding site for the glucocorticoid receptor. Receptor binding to the nGRE was correlated to hormone-dependent repression by using promoter mutagenesis. The nGRE was also shown to contain a binding site for a nuclear protein of the COUP family of transcription factors. Since the binding sites for COUP and the glucocorticoid receptor overlap, glucocorticoid-dependent repression of POMC transcription may result from mutually exclusive binding of these two nuclear transcription factors.