Evidence map›Paper›PMID 19171160›Full record

Trial reportSteroids

Simultaneous quantification of GABAergic 3alpha,5alpha/3alpha,5beta neuroactive steroids in human and rat serum.

Patrizia Porcu, Todd K O'Buckley, Sarah E Alward, Christine E Marx, Lawrence J Shampine, Susan S Girdler, A Leslie Morrow

Open access · greenAbstract readClinical Trial
In one paragraph

Trial report in Steroids. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
1.1field-weighted citation impact, top 28% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

43 citing papers in PubMed, 64 citations in OpenAlex.

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  12. Dynamic Adaptation in Neurosteroid Networks in Response to Alcohol.Handbook of experimental pharmacology · 2018
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Patrizia PorcuDepartment of Psychiatry and Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7178, USA.
Todd K O'Buckley
Sarah E Alward
Christine E Marx
Lawrence J Shampine
Susan S Girdler
A Leslie Morrow
University of North Carolina at Chapel Hill · USDuke Medical Center · USDuke University Hospital · US

Funding

NEUROENDOCRINE MODULATION OF STRESS RESPONSES IN PMSR01MH051246 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI GIRDLER, SUSAN S. · 1995 to 2011
$3.5M
NEUROSTEROIDS AND ETHANOL INTERACTIONSR37AA010564 · NIAAA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI MORROW, A LESLIE · 2000 to 2009
$2.7M
INIA: Consortium-Bioanalytical CoreU01AA013515 · NIAAA · UNIVERSITY OF MEMPHIS · PI SUTTER, THOMAS R · 2002 to 2006
$2.4M
Stress, alcohol and GABAergic neuroactive steroids in primatesU01AA016672 · NIAAA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI MORROW, A LESLIE · 2007 to 2011
$1.4M
Alcohol-induced epigenetic changes in the liver genomeR21AA016677 · NIAAA · OHIO STATE UNIVERSITY · PI JACOB, SAMSON T · 2006 to 2007
$401k
NEUROSTEROIDS AND ETHANOL DEPENDENCER01AA010564 · NIAAA · UNIVERSITY OF NORTH CAROLINA CHAPEL HILL · PI MORROW, A LESLIE · 1996 to 1997
–
NIAAA NIH HHS R01 AA010564NIAAA NIH HHS R21 AA016677NIAAA NIH HHS R37 AA010564NIAAA NIH HHS U01 AA013515NIAAA NIH HHS U01 AA016672NIAAA NIH HHS UO1 AA013515NIAAA NIH HHS UO1 AA016677NIMH NIH HHS R01 MH051246
6 · The paper itself

Abstract

The 3alpha,5alpha- and 3alpha,5beta-reduced derivatives of progesterone, deoxycorticosterone, dehydroepiandrosterone and testosterone enhance GABAergic neurotransmission and produce inhibitory neurobehavioral and anti-inflammatory effects. Despite substantial information on the progesterone derivative (3alpha,5alpha)-3-hydroxypregnan-20-one (3alpha,5alpha-THP, allopregnanolone), the physiological significance of the other endogenous GABAergic neuroactive steroids has remained elusive. Here, we describe the validation of a method using gas chromatography-mass spectrometry to simultaneously identify serum levels of the eight 3alpha,5alpha- and 3alpha,5beta-reduced derivatives of progesterone, deoxycorticosterone, dehydroepiandrosterone and testosterone. The method shows specificity, sensitivity and enhanced throughput compared to other methods already available for neuroactive steroid quantification. Administration of pregnenolone to rats and progesterone to women produced selective effects on the 3alpha,5alpha- and 3alpha,5beta-reduced neuroactive steroids, indicating differential regulation of their biosynthetic pathways. Pregnenolone administration increased serum levels of 3alpha,5alpha-THP (+1488%, p<0.001), (3alpha,5alpha)-3,21-dihydroxypregnan-20-one (3alpha,5alpha-THDOC, +205%, p<0.01), (3alpha,5alpha)-3-hydroxyandrostan-17-one (3alpha,5alpha-A, +216%, p<0.001), (3alpha,5alpha,17beta)-androstane-3,17-diol (3alpha,5alpha-A-diol, +190%, p<0.01). (3alpha,5beta)-3-hydroxypregnan-20-one (3alpha,5beta-THP) and (3alpha,5beta)-3-hydroxyandrostan-17-one (3alpha,5beta-A) were not altered, while (3alpha,5beta)-3,21-dihydroxypregnan-20-one (3alpha,5beta-THDOC) and (3alpha,5beta,17beta)-androstane-3,17-diol (3alpha,5beta-A-diol) were increased from undetectable levels to 271+/-100 and 2.4+/-0.9 pg+/-SEM, respectively (5/8 rats). Progesterone administration increased serum levels of 3alpha,5alpha-THP (+1806%, p<0.0001), 3alpha,5beta-THP (+575%, p<0.001), 3alpha,5alpha-THDOC (+309%, p<0.001). 3alpha,5beta-THDOC levels were increased by 307%, although this increase was not significant because this steroid was detected only in 3/16 control subjects. Levels of 3alpha,5alpha-A, 3alpha,5beta-A and pregnenolone were not altered. This method can be used to investigate the physiological and pathological role of neuroactive steroids and to develop biomarkers and new therapeutics for neurological and psychiatric disorders.

Indexed as

AnimalsCalibrationFemalegamma-Aminobutyric AcidGas Chromatography-Mass SpectrometryHumansMalePregnenoloneProgesteroneRatsRats, Sprague-DawleyReference StandardsReproducibility of ResultsSteroidsgamma-Aminobutyric AcidPregnenoloneProgesteroneSteroids

Identifiers

PMID19171160
PMCPMC2832187
OpenAlexW1982298951

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.