title: Complex regulatory interactions control CRH gene expression.
abstract: 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.
authors.affiliation: Mothers and Babies Research Centre, Hunter Medical Research Institute, University of Newcastle, NSW 2310, Australia. Rick.Nicholson@hunter.health.nsw.gov.au
authors.forename: Richard C
authors.initials: RC
authors.lastname: Nicholson
authors.forename: Bruce R
authors.initials: BR
authors.lastname: King
authors.forename: Roger
authors.initials: R
authors.lastname: Smith
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D051379:Mice; D010920:Placenta / Q000378:metabolism; D020218:Response Elements / Q000502:physiology*; D014407:Tumor Cells, Cultured
chemical_list: D003346:Corticotropin-Releasing Hormone