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Corticotroph isolation from Pomc-eGFP mice reveals sustained transcriptional dysregulation characterising a mouse model of glucocorticoid-induced suppression of the Hypothalamus-Pituitary-Adrenal axis

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to receive DEX (~0.4 mg/kg bodyweight/day) or vehicle via drinking water for 4 weeks following which treatment was withdrawn and tissues were harvested after another 0, 1, and 4 weeks.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

Publication metadata

Author(s): Duncan PJ, McClafferty H, Nolan O, Ding Q, Homer NZM, Le Tissier P, Walker BR, Shipston MJ, RomanĂ² N, Chambers TJG

Publication type: Article

Publication status: Published

Journal: Journal of Neuroendocrinology

Year: 2022

Pages: ePub ahead of Print

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


DOI: 10.1111/jne.13165


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Funder referenceFunder name
Wellcome Trust