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Lookup NU author(s): Professor Brian WalkerORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Glucocorticoids (GC) are prescribed for periods >3 months to 1-3% of the UK population; 10-50% of these patients develop hypothalamus-pituitary-adrenal (HPA) axis suppression, which may last over 6 months and is associated with morbidity and mortality. Recovery of the pituitary and hypothalamus is necessary for recovery of adrenal function. We developed a mouse model of Dexamethasone (DEX)-induced HPA axis dysfunction in order to further explore recovery in the pituitary. Adult male wild-type C57BL6/J or Pomc-eGFP transgenic mice were randomly assigned to receive DEX (~0.4 mg/kg bodyweight/day) or vehicle via drinking water for 4 weeks following which treatment was withdrawn and tissues were harvested after another 0, 1, and 4 weeks. Corticotrophs were isolated from Pomc-eGFP pituitaries using FACS, and RNA extracted for RNA-seq. DEX treatment suppressed corticosterone production, which remained partially suppressed at least 1 week following DEX withdrawal. In the adrenal, Hsd3b2, Cyp11a1, and Mc2r mRNA levels were significantly reduced at time 0, with Mc2r and Cyp11a1 remaining reduced 1 week following DEX withdrawal. The corticotroph transcriptome was modified by DEX treatment with some differences between groups persisting 4 weeks following withdrawal. No genes supressed by DEX exhibited ongoing attenuation 1- and 4-weeks following withdrawal, whilst only 2 genes were upregulated and remained so following withdrawal. A pattern of rebound at 1 and 4 weeks was observed in 14 genes that increased following suppression, and 6 genes that were reduced by DEX and then increased. Chronic GC treatment may induce persistent changes in the pituitary that may influence future response to GC treatment or stre
Author(s): Duncan PJ, McClafferty H, Nolan O, Ding Q, Homer NZM, Le Tissier P, Walker BR, Shipston MJ, Romanò N, Chambers TJG
Publication type: Article
Publication status: Published
Journal: Journal of Neuroendocrinology
Year: 2022
Volume: 34
Issue: 7
Online publication date: 14/07/2022
Acceptance date: 18/04/2022
Date deposited: 16/05/2022
ISSN (print): 0953-8194
ISSN (electronic): 1365-2826
Publisher: Wiley
URL: https://doi.org/10.1111/jne.13165
DOI: 10.1111/jne.13165
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