IMR Press / FBL / Volume 9 / Issue 1 / DOI: 10.2741/1204

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Complex regulatory interactions control CRH gene expression
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1 Mothers and Babies Research Centre, Hunter Medical Research Institute, University of Newcastle, NSW 2310, Australia
Academic Editor:John Leah
Front. Biosci. (Landmark Ed) 2004, 9(1), 32–39; https://doi.org/10.2741/1204
Published: 1 January 2004
(This article belongs to the Special Issue Regulation of gene expression in the brain)
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.

Keywords
Peptide Hormone
Hypothalamus
Transcription factors
CREB
Fos
Glucocorticoids
Steroid Hormone
Gene Promoter
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