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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Mol. Neurosci. | doi: 10.3389/fnmol.2019.00259

Rapid Action of Retinoic Acid on the Hypothalamic Pituitary Adrenal Axis

  • 1The Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, United Kingdom
  • 2Okinawa Institute of Science and Technology Graduate University, Japan

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.

Keywords: Retinoic acid, Hypothalamic pituitary adrenal (HPA) axis, Corticosterone, adrenal gland, Aldosterone synthesis, CYP11B1, CYP11B2

Received: 25 Aug 2018; Accepted: 10 Oct 2019.

Copyright: © 2019 Imoesi, Bowman, Stoney, Matz and McCaffery. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Peter McCaffery, The Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, AB24 3FX, Scotland, United Kingdom, p.j.mccaffery@abdn.ac.uk