title: Advances in understanding corticotrophin-releasing hormone gene expression.
abstract: Glucocorticoids inhibit corticotrophin-releasing hormone (CRH) gene expression in the hypothalamic paraventricular nucleus (PVN), but stimulate expression in the placenta. In AtT20 cells (a model of PVN CRH production) cAMP produces a high level of promoter activity. Cyclic AMP stimulation occurs through the cAMP response element (CRE) and the caudal type homeobox protein response element (CDXARE). The CRE acts as part of a cAMP response unit that includes the hybrid steroid response element (HRE), ecdysone response element (EcRE), metal-responsive transcription factor-1 response element (MTFRE), ying yang 1 response element (YY1RE) and negative glucocorticoid response element (nGRE). Cyclic AMP acts on the HRE, EcRE and MTFRE to block YY1RE mediated inhibition of the CRE. Glucocorticoids acting at the nGRE inhibit cAMP activation of the CRE. In placental cells the CRH promoter has low intrinsic basal activity and cAMP causes a modest increase in activity. Stimulation by glucocorticoids and cAMP and inhibition by estrogen and estrogen receptor alpha occurs through the CRE. In AtT20 cells multiple response elements coordinate a response to cAMP and glucocorticoids while in placental cells the CRE acts in isolation. These differences in promoter function lead to responses that meet specific physiological needs.
authors.affiliation: Department of Endocrinology, Mothers and Babies Research Centre, John Hunter Hospital and University of Newcastle, Newcastle, NSW 2310, Australia. Bruce.King@hnehealth.nsw.gov.au
authors.forename: Bruce R
authors.initials: BR
authors.lastname: King
authors.forename: Richard C
authors.initials: RC
authors.lastname: Nicholson
mesh_terms: D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D010920:Placenta / Q000378:metabolism; D011401:Promoter Regions, Genetic; D020218:Response Elements
chemical_list: D004268:DNA-Binding Proteins; D003346:Corticotropin-Releasing Hormone