Rapid Action of Retinoic Acid on the Hypothalamic Pituitary Adrenal Axis

Peter I Imoesi, Ellen E Bowman, Patrick Niall Stoney, Sylwia Matz, Peter McCaffery* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticle

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Abstract

Retinoic acid is the active metabolite of vitamin A but is also used as a medication, primarily for acne in which the treatment regime lasts several months. A number of studies have indicated that treatment with retinoic acid over this time period impacts the hypothalamic-pituitary-adrenal (HPA) axis and may contribute to a number of the side-effects of the drug. No studies though have investigated the short-term, early effects retinoic acid may have on the HPA axis via the transcriptional pathways activated by the retinoic acid receptor. This study investigated the action of retinoic acid over 3 days on regulatory components of the HPA axis. Several key genes involved in glucocorticoid feedback pathways in the hippocampus, hypothalamus and pituitary were unchanged after 3-days exposure to retinoic acid. Key elements though in the adrenal gland involved in corticosterone and aldosterone synthesis were altered in particular with the Cyp11b2 gene downregulated in-vivo and ex-vivo. The rapid, 5 hours, change in Cyp11b2 expression suggested this activation may be direct. These results highlight the adrenal gland as a target of short-term action of retinoic acid and potentially a trigger component in the mechanisms by which the long-term adverse effects of retinoic acid treatment occur.

Original languageEnglish
Article number259
Number of pages8
JournalFrontiers in Neuroscience
Volume12
DOIs
Publication statusPublished - 30 Oct 2019

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Keywords

  • retinoic acid
  • Hypothalamic pituitary adrenal (HPA) axis
  • Corticosterone
  • adrenal gland
  • Aldosterone synthesis
  • CYP11B1
  • CYP11B2
  • Chronic traumatic encephalopathy
  • TDP-43
  • Amyotrophic lateral sclerosis
  • Microtubule associated tau protein
  • Frontotemporal dementia

ASJC Scopus subject areas

  • Neuroscience(all)

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