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Metabolism of neuroactive steroids in day-old chick brain

Sujkovic, E; Mileusnic, R; Fry, JP; (2009) Metabolism of neuroactive steroids in day-old chick brain. Journal of Neurochemistry , 109 (2) 348 - 359. 10.1111/j.1471-4159.2009.05965.x. Green open access

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Abstract

Metabolism of the neuroactive steroids pregnenolone (PREG), progesterone (PROG), dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS) was investigated in day-old chick brain following direct injection of the H-3-labelled compounds into the intermediate medial mesopallium and sampling at times known to be crucial for memory formation in this brain region. H-3-label from these steroids was cleared rapidly from the brain, decreasing to barely detectable levels within 5 h. Following extraction and fractionation, the H-3-labelled brain steroids were identified by TLC, coupled with acetylation and/or separation in different solvent systems. PREG and PROG were converted within 10 min mostly to 20 beta-dihydropregnenolone (20 beta-DHPREG) and 5 beta-dihydroprogesterone, respectively. There was no detectable metabolism of DHEA. Label from DHEAS persisted for longer (half-time 18.9 min) than the free steroid but with no detectable metabolism other than a small amount (4%) of desulphation to DHEA. Further investigation of chick brain steroid metabolism by incubation of subcellular fractions (1-3 h, 37 degrees C) with PREG, PROG or DHEA plus NADPH led to the formation of the following compounds: 20 beta-DHPREG from PREG (particularly in cytosol); 5 beta-dihydroprogesterone and 3 alpha,5 beta-tetrahydroprogesterone from PROG and no detectable metabolism of DHEA. Following incubation of the same brain fractions and labelled steroids with NAD(+), there was no detectable metabolism of PREG or PROG but some conversion of DHEA to androstenedione, especially in the nuclear fraction. The results suggest direct actions of DHEA(S) on the early stages of memory formation in the chick and introduce the possibility that PREG may act indirectly via 20 beta-DHPREG.

Type: Article
Title: Metabolism of neuroactive steroids in day-old chick brain
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/j.1471-4159.2009.05965.x
Publisher version: http://dx.doi.org/10.1111/j.1471-4159.2009.05965.x
Language: English
Additional information: This is the peer reviewed version of the following article: Sujkovic, E; Mileusnic, R; Fry, JP; (2009) Metabolism of neuroactive steroids in day-old chick brain. Journal of Neurochemistry, 109 (2) 348 - 359, which has been published in final form at: http://dx.doi.org/10.1111/j.1471-4159.2009.05965.x. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving (http://olabout.wiley.com/WileyCDA/Section/id-828039.html#terms).
Keywords: brain, chicks, dehydroepiandrosterone, pregnenolone, progesterone, steroid, central nervous system, rat brain, dehydroepiandrosterone-sulfate, quail brain, testosterone metabolism, model system, zebra finch, neurosteroids, pregnenolone, memory
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/54723
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