PMID- 21463644 OWN - NLM STAT- MEDLINE DCOM- 20111014 LR - 20211020 IS - 1873-507X (Electronic) IS - 0031-9384 (Print) IS - 0031-9384 (Linking) VI - 104 IP - 2 DP - 2011 Aug 3 TI - Histone deacetylase 1 (HDAC1) participates in the down-regulation of corticotropin releasing hormone gene (crh) expression. PG - 312-20 LID - 10.1016/j.physbeh.2011.03.026 [doi] AB - The paraventricular nucleus of the hypothalamus (PVH) plays a central role in regulating the hypothalamic-pituitary-adrenal (HPA) axis. Medial parvocellular neurons of the PVH (mpPVH) integrate sensory and humoral inputs to maintain homeostasis. Humoral inputs include glucocorticoids secreted by the adrenals, which down-regulate HPA activation. A primary glucocorticoid target is the population of mpPVH neurons that synthesize and secrete corticotropin-releasing factors, the most potent of which is corticotropin-releasing hormone (CRH). Although CRH gene (crh) expression is known to be down-regulated by glucocorticoids, the mechanisms by which this process occurs are still poorly understood. To begin this study we postulated that glucocorticoid repression of crh involves HDAC recruitment to the region of the crh proximal promoter. To evaluate this hypothesis, we treated hypothalamic cells that express CRH with the HDAC inhibitor trichostatin A (TSA). As predicted, treatment with TSA led to increased CRH mRNA levels and crh promoter activity. Although co-treatment with Dex (10(-7)M) reduced the TSA effect on mRNA levels, it failed to reduce promoter activity; however co-transfection of HDAC1 but not 3 restored Dex inhibition. A distinction between HDAC1 and 3 was also apparent with respect to crh promoter occupancy. Dex led to increased HDAC1 but not HDAC3 occupancy. In vivo studies revealed that CRH-immunoreactive (-ir) neurons contained HDAC1- and HDAC3-ir. Collectively, these data point to a role for HDAC1 in the physiologic regulation of crh. CI - Copyright (c) 2011 Elsevier Inc. All rights reserved. FAU - Miller, Lydia AU - Miller L AD - Department of Pathology, University of Virginia, 415 Lane Road, Charlottesville, VA 22908, USA. FAU - Foradori, Chad D AU - Foradori CD FAU - Lalmansingh, Avin S AU - Lalmansingh AS FAU - Sharma, Dharmendra AU - Sharma D FAU - Handa, Robert J AU - Handa RJ FAU - Uht, Rosalie M AU - Uht RM LA - eng GR - R01 MH082900/MH/NIMH NIH HHS/United States GR - R01 MH082900-01A2/MH/NIMH NIH HHS/United States GR - R01 MH82900/MH/NIMH NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20110401 PL - United States TA - Physiol Behav JT - Physiology & behavior JID - 0151504 RN - 0 (Glucocorticoids) RN - 0 (Histone Deacetylase Inhibitors) RN - 0 (Hydroxamic Acids) RN - 0 (RNA, Messenger) RN - 3X2S926L3Z (trichostatin A) RN - 7S5I7G3JQL (Dexamethasone) RN - 9015-71-8 (Corticotropin-Releasing Hormone) RN - EC 3.5.1.98 (Histone Deacetylase 1) RN - EC 3.5.1.98 (Histone Deacetylases) SB - IM MH - Adrenalectomy MH - Analysis of Variance MH - Animals MH - Cell Line MH - Chromatin Immunoprecipitation MH - Corticotropin-Releasing Hormone/*genetics/metabolism MH - Dexamethasone/pharmacology MH - Down-Regulation/drug effects/*physiology MH - Drug Interactions MH - Glucocorticoids/pharmacology MH - Histone Deacetylase 1/*metabolism MH - Histone Deacetylase Inhibitors/pharmacology MH - Histone Deacetylases/genetics/metabolism MH - Hydroxamic Acids/pharmacology MH - Male MH - Paraventricular Hypothalamic Nucleus/drug effects/*enzymology MH - RNA, Messenger/*metabolism MH - Rats MH - Rats, Sprague-Dawley PMC - PMC3650854 MID - NIHMS287312 EDAT- 2011/04/06 06:00 MHDA- 2011/10/15 06:00 PMCR- 2013/05/10 CRDT- 2011/04/06 06:00 PHST- 2011/01/13 00:00 [received] PHST- 2011/03/10 00:00 [revised] PHST- 2011/03/25 00:00 [accepted] PHST- 2011/04/06 06:00 [entrez] PHST- 2011/04/06 06:00 [pubmed] PHST- 2011/10/15 06:00 [medline] PHST- 2013/05/10 00:00 [pmc-release] AID - S0031-9384(11)00145-4 [pii] AID - 10.1016/j.physbeh.2011.03.026 [doi] PST - ppublish SO - Physiol Behav. 2011 Aug 3;104(2):312-20. doi: 10.1016/j.physbeh.2011.03.026. Epub 2011 Apr 1.