Postnatal hypercortisolism: short and long-term consequences

Abstract

Event Abstract Back to Event Postnatal hypercortisolism: short and long-term consequences Mathias Schmidt1* 1 Max Planck Institute of Psychiatry, Germany A tight regulation of hypothalamic-pituitary-adrenal axis activity is essential for successful adaptation to stressful stimuli and disruption of negative feedback has been implicated in a number of human disease conditions. Early trauma, in particular, is a main risk factor for diseases such as post-traumatic stress disorder or depression, but the molecular mechanisms that lead to these long-term consequences are poorly understood. Here we test the hypotheses that the pituitary glucocorticoid receptor (GR) is involved in regulating HPA axis function in neonatal and adult animals. Further we investigate whether postnatal hypercortisolism induced by pituitary GR deficiency is a main factor contributing to the persistent effects of early life stress. Conditional knockout mice with a deletion of the GR at the pituitary (GRPOMCCre) show excessive basal corticosterone levels during postnatal development, but not in adulthood. The hypercortisolemic state of neonatal GRPOMCCre mice is accompanied by central gene expression changes of corticotropin-releasing hormone and vasopressin in the paraventricular nucleus, but these alterations normalize at later ages. In adult mice, pituitary GR deficiency results in impaired glucocorticoid negative feedback. Further, adult GRPOMCCre mice display a more active coping strategy in the forced swim test, with no alterations in anxiety-like behaviour or cognitive functions. Postnatal GR antagonist treatment is able to prevent the long-term behavioural effects in GRPOMCCre mice. In conclusion, we show that pituitary GRs are centrally involved in regulating HPA axis activity in neonates and mediate negative feedback regulation in adult animals. Postnatal glucocorticoid excess results in an altered stress-coping behaviour in adult animals, with no significant effects on anxiety-like behaviour or cognition. Conference: 41st European Brain and Behaviour Society Meeting, Rhodes Island, Greece, 13 Sep - 18 Sep, 2009. Presentation Type: Oral Presentation Topic: Stress satellite symposium lectures Citation: Schmidt M (2009). Postnatal hypercortisolism: short and long-term consequences. Conference Abstract: 41st European Brain and Behaviour Society Meeting. doi: 10.3389/conf.neuro.08.2009.09.077 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 05 Jun 2009; Published Online: 05 Jun 2009. * Correspondence: Mathias Schmidt, Max Planck Institute of Psychiatry, Munich, Germany, schmidt_mathias@gmx.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Mathias Schmidt Google Mathias Schmidt Google Scholar Mathias Schmidt PubMed Mathias Schmidt Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.