Glucocorticoid sensitizers Bag1 and Ppid are regulated by adolescent stress in a sex-dependent manner

• Type of Material: Article
• Authors: Chase H. Bourke, Emory University; Madiha Q. Raees, Emory University; Sanjana Malviya, Emory University; Cory A. Bradburn, Emory University; Elisabeth B. Binder, Emory University; Gretchen Neigh, Emory University
• Language: English
• Date: 2013-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 Elsevier Ltd. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.psyneuen.2012.05.001
• Title of Journal or Parent Work: Psychoneuroendocrinology
• ISSN: 0306-4530
• Volume: 38
• Issue: 1
• Start Page: 84
• End Page: 93
• Grant/Funding Information: GN Neigh receives grant funding from NIMH, AHA, NARSAD, GSK, and Emory University.; Funding for this study was provided by Emory University’s Comprehensive Neurosciences Center’s Child and Adolescent Mood Program and salary support for CH Bourke was provided by the NIEHS (Grant Number: T32 ES012870, the HHMI Med into Grad Program (Grant Number: 5600672) and the NCRR Atlanta Clinical and Translational Science Institute (Grant Number: UL1 RR025008).; EB Binder receives funding from NIMH, the Doris Duke Charitable Foundation, the Behrens-Weise foundation, the NeuroNova G GmbH and PharmaNeuroBoost.
• Keywords: social defeat; Ncoa1; Cyp40; adolescent stress; Fkbp51
• Research Categories: Psychology, Behavioral

Abstract

Early life stress precipitates dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and this effect is most pronounced in females. The mechanisms that mediate female sensitivity to stress-induced HPA axis dysregulation are unknown. The purpose of this study was to determine whether sex moderates the effects of chronic adolescent stress on glucocorticoid receptor (GR) translocation and moderators of the GR system. Female adolescent rats with a history of chronic stress exposure demonstrated a delayed resolution of the plasma corticosterone response to an acute stressor and this delay was accompanied by attenuated GR translocation compared to control adolescent females. The chronic stress-induced phenotype in females was similar to the baseline phenotype in male adolescent rats. Conversely, the expression patterns of GR moderators/co-chaperones became more sexually dimorphic following chronic stress, suggesting divergent function of the GR system between male and female adolescent rats. Gene expression of Ppid, a positive regulator of the GR, was predicted by plasma estradiol and 34% lower in control adolescent females than males, indicating that sex steroids may play a role in the sexually dimorphic response. After chronic adolescent stress, females displayed elevated hippocampal expression of Bag1 and Ppid genes that was not observed in males. Overall, the GR output to an acute stressor, illustrated by transcription of Nr3c1 (encoding the GR), Bag1, Fkbp5, Ppid, and Src1, was significantly upregulated and differed in a sex-specific and chronic stress-dependent manner. This study provides new evidence for sex differences during development and adaptation of the glucocorticoid receptor chaperone system.