Chronic psychosocial stress results in sensitization of the HPA axis to acute heterotypic stressors despite a reduction of adrenal in vitro ACTH responsiveness

Uschold-Schmidt, Nicole and Nyuyki, Kewir D. and Fuechsl, Andrea M. and Neumann, Inga D. and Reber, Stefan O. (2012) Chronic psychosocial stress results in sensitization of the HPA axis to acute heterotypic stressors despite a reduction of adrenal in vitro ACTH responsiveness. PSYCHONEUROENDOCRINOLOGY, 37 (10). pp. 1676-1687. ISSN 0306-4530,

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Abstract

Although chronic psychosocial stress is often accompanied by changes in basal hypothalamo-pituitary-adrenal (HPA) axis activity, it is vital for a chronically-stressed organism to mount adequate glucocorticoid (GC) responses when exposed to acute challenges. The main aim of the present study was to test whether this is true or not for the chronic subordinate colony housing (CSC, 19 days) paradigm, an established and clinically relevant mouse model of chronic psychosocial stress. As shown previously, CSC mice are characterized by unaffected morning and decreased evening plasma corticosterone (CORT) levels despite enlarged adrenals, suggesting a maladaptive breakdown of adrenal functioning. Plasma CORT levels, determined by repeated blood sampling via jugular vein catheters, as well as relative right adrenal CORT content were increased in CSC compared with single-housed control (SHC) mice in response to acute elevated platform (EPF, 5 min) exposure. However, in vitro stimulation of adrenal explants with physiological and pharmacological doses of ACTH revealed an attenuated responsiveness of both the left and right adrenal glands following CSC, despite mRNA and/or protein expression of melanocortin 2 receptor (Mc2r), Mc2r accessory protein (MRAP), and key enzymes of steroidogenesis were not down-regulated. Taken together, we show that chronic psychosocial stressor exposure impairs in vitro ACTH responsiveness of both the left and right adrenal glands, whereas it increases adrenal responsiveness to an acute heterotypic stressor in vivo. This suggests that an additional factor present during acute stressor exposure in vivo rescues left and right adrenal ACTH sensitivity, or itself acts as CORT secretagogue in chronically stressed CSC mice. (C) 2012 Elsevier Ltd. All rights reserved.

Item Type: Article
Uncontrolled Keywords: PITUITARY-ADRENOCORTICAL AXIS; GLUCOCORTICOID DEFICIENCY TYPE-2; SPLANCHNIC NERVE-STIMULATION; TERM VOLUNTARY EXERCISE; REPEATED SOCIAL DEFEAT; GENE-EXPRESSION; GLOMERULOSA CELLS; PLASMA OXYTOCIN; INDUCED COLITIS; NEUROPEPTIDE-Y; Chronic psychosocial stress; CSC; Heterotypic stressor; HPA axis; Adrenal glands; ACTH
Subjects: 500 Science > 570 Life sciences
500 Science > 590 Zoological sciences
Divisions: Biology, Preclinical Medicine > Institut für Zoologie
Biology, Preclinical Medicine > Institut für Zoologie > Tierphysiologie/Neurobiologie (Prof. Dr. Inga Neumann)
Depositing User: Dr. Gernot Deinzer
Date Deposited: 06 May 2020 04:53
Last Modified: 06 May 2020 04:53
URI: https://pred.uni-regensburg.de/id/eprint/18066

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