- Title
- Complex regulatory interactions control CRH gene expression
- Creator
- Nicholson, Richard C.; King, Bruce R.; Smith, Roger
- Relation
- Frontiers in Bioscience Vol. 9, p. 32-39
- Publisher Link
- http://dx.doi.org/10.2741/1204
- Publisher
- Frontiers in Bioscience
- Resource Type
- journal article
- Date
- 2004
- Description
- Glucocorticoids inhibit corticotrophin releasing hormone (CRH) production in the hypothalamus but stimulate production from the placenta. To identify key elements regulating the CRH gene, mouse pituitary tumor-derived cells (AtT20 cells) were used as a hypothalamic model in an analysis of the CRH promoter. Two cAMP responsive elements were identified: (I) a consensus cAMP response element (CRE) and (II) a previously unrecognized caudal-type homeobox response element (CDXRE). Glucocorticoids inhibit only the component of cAMP-stimulation occurring via the CRE through an action involving a negative glucocorticoid response element (nGRE). We also identified two regions that, in the absence of the nGRE, can be stimulated by glucocorticoids: (I) the CRE and (II) a region between -213 to -99bps. Electrophoretic mobility shift assays identified binding of the transcription factors CREB and Fos at the CRE in AtT20 cells, whereas CREB and cJun were detected in placental cells. In addition, a novel CRE-binding transcription factor has been identified that is expressed in the brain and in placenta. A model is presented whereby CRH gene regulation is mediated via tissue specific expression of transcription factors.
- Subject
- glucocorticoids; corticotrophin releasing hormone production; hypothalamus; CRH gene expression
- Identifier
- http://hdl.handle.net/1959.13/33308
- Identifier
- uon:3174
- Identifier
- ISSN:1093-9946
- Language
- eng
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