Journal article
5α-reduced neurosteroids sex-dependently reverse central prenatal programming of neuroendocrine stress responses in rats
PJ Brunton, MV Donadio, ST Yao, M Greenwood, JR Seckl, D Murphy, JA Russell
Journal of Neuroscience | Published : 2015
Open access
Abstract
Maternal social stress during late pregnancy programs hypothalamo-pituitary-adrenal (HPA) axis hyper-responsiveness to stressors, such that adult prenatally stressed (PNS) offspring display exaggerated HPA axis responses to a physical stressor (systemic interleukin-1β; IL-1β) in adulthood, compared with controls. IL-1β acts via a noradrenergic relay from the nucleus tractus solitarii (NTS) to corticotropin releasing hormone neurons in the paraventricular nucleus (PVN). Neurosteroids can reduce HPA axis responses, so allopregnanolone and 3β- androstanediol (3β-diol; 5α-reduced metabolites of progesterone and testosterone, respectively) were given subacutely (over 24 h) to PNS rats to seek rev..
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Awarded by Biotechnology and Biological Sciences Research Council
Funding Acknowledgements
This work was supported by the BBSRC, UK: BB/C518957/1 (P.J.B., J.A.R.), BB/J004332/1 (P.J.B.), BB/G006156/1 (M.G., S.T.Y., D.M); CAPES, Brazil (M.V.D.); British Heart Foundation (M.G., S.T.Y., D.M.); and The University of Malaya (HIR Award H-20001-E000086, D.M.). We thank Helen Cameron for technical assistance; undergraduate students, Robert Browning and Carly Schott assisted in some experiments;Megan Holmes (University of Edinburgh. UK) for providing the plasmids containing the rat CRY and ER-beta cDNA; Marcel Karperien and Dr Jakomijn Hoogendam (University of Leiden, The Netherlands) for providing the plasmid containing 5 alpha-reductase-1 cDNA; Trevor Penning (University of Pennsylvania, Philadelphia, PA) for providing the plasmid containing 3 alpha-hydroxysteroid dehydrogenase cDNA; and J. Ian Mason (University of Edinburgh, UK)for providing cDNA encoding 5 alpha-reductase-1.