AUTHOR=Imoesi Peter I. , Bowman Ellen E. , Stoney Patrick N. , Matz Sylwia , McCaffery Peter 

TITLE=Rapid Action of Retinoic Acid on the Hypothalamic Pituitary Adrenal Axis

JOURNAL=Frontiers in Molecular Neuroscience

VOLUME=Volume 12 - 2019

YEAR=2019

URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2019.00259

DOI=10.3389/fnmol.2019.00259

ISSN=1662-5099

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.