17beta-Estradiol is required for the sexually dimorphic effects of repeated binge-pattern alcohol exposure on the HPA axis during adolescence. Journal Article


Authors: Przybycien-Szymanska, M. M.; Gillespie, R. A.; Pak, T. R.
Article Title: 17beta-Estradiol is required for the sexually dimorphic effects of repeated binge-pattern alcohol exposure on the HPA axis during adolescence.
Abstract: Alcohol consumption during adolescence has long-term sexually dimorphic effects on anxiety behavior and mood disorders. We have previously shown that repeated binge-pattern alcohol exposure increased the expression of two critical central regulators of stress and anxiety, corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP), in adolescent male rats. By contrast, there was no effect of alcohol on these same genes in adolescent females. Therefore, we tested the hypothesis that 17beta-estradiol (E(2)), the predominant sex steroid hormone in females, prevents alcohol-induced changes in CRH and AVP gene expression in the paraventricular nucleus (PVN) of the hypothalamus. To test this hypothesis, postnatal day (PND) 26 females were ovariectomized and given E(2) replacement or cholesterol as a control. Next, they were given an alcohol exposure paradigm of 1) saline alone, 2) acute (single dose) or 3) a repeated binge-pattern. Our results showed that acute and repeated binge-pattern alcohol treatment increased plasma ACTH and CORT levels in both E(2)- and Ch-treated groups, however habituation to repeated binge-pattern alcohol exposure was evident only in E(2)-treated animals. Further, repeated binge-pattern alcohol exposure significantly decreased CRH and AVP mRNA in Ch-, but not E(2)-treated animals, which was consistent with our previous observations in gonad intact females. We further tested the effects of E(2) and alcohol treatment on the activity of the wild type CRH promoter in a PVN-derived neuronal cell line. Alcohol increased CRH promoter activity in these cells and concomitant treatment with E(2) completely abolished the effect. Together our data suggest that E(2) regulates the reactivity of the HPA axis to a repeated stressor through modulation of the habituation response and further serves to maintain normal steady state mRNA levels of CRH and AVP in the PVN in response to a repeated alcohol stressor.
Journal Title: PloS one
Volume: 7
Issue: 2
ISSN: 1932-6203; 1932-6203
Publisher: Unknown  
Journal Place: United States
Date Published: 2012
Start Page: e32263
Language: English
DOI/URL:
Notes: ID: 12464; Record Owner: From MEDLINE, a database of the U.S. National Library of Medicine.; Status: MEDLINE; Publishing Model: Journal available in: Print-Electronic Citation processed from: Internet; NLM Journal Code: 101285081; Other ID: Source: NLM. PMC3284554; CAS Registry/EC Number/Name of Substance: 0 (RNA, Messenger). 50-28-2 (Estradiol). 64-17-5 (Ethanol). 9015-71-8 (Corticotropin-Releasing Hormone).; Grant Number: R21AA018398 (United States NIAAA NIH HHS), T32 AA013527 (United States NIAAA NIH HHS); Electronic Date of Publication: 20120222; Entry Date: 20120827