The identification and simultaneous quantification of neuroactive androstane steroids and their polar conjugates in the serum of adult men, using gas chromatography–mass spectrometry

Kancheva, Lyudmila; Hill, Martin; Včeláková, Helena; Vrbíková, Jana; Pelikánová, Terezie; Stárka, L.

doi:10.1016/j.steroids.2007.06.006

Cited by 10 publications

(9 citation statements)

References 48 publications

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“…The ability to measure all eight GABAergic neuroactive steroids from the same 300 μl aliquot of serum is particularly useful when only small volumes of sample can be obtained (frequently the case in clinical studies). The intra- and inter-assay variability and sensitivity are similar to previous published work for 3α,5α-THP[46,50], 3α,5β-THP[46], 3α,5α-A[47], 3α,5β-A[47], 3α,5α-A-diol[47], 3α,5β-A-diol[47] and pregnenolone[46,47,50,51] in serum. No data is available for 3α,5α-THDOC and 3α,5β-THDOC.…”

Section: Discussionsupporting

confidence: 86%

“…While the sensitivity of the assay for 3α,5α-THP is comparable to some previous studies[46,50], other authors have reported slightly better sensitivity using HPLC purification prior to GC-MS[29] or better sensitivity to 3α,5α-THP, 3α,5α-A and 3α,5β-A using different GC-MS settings[47], but direct comparisons of solid phase purification vs. HPLC purification or the different GC-MS settings have yet to be performed and are needed to determine which approach offers more sensitivity. The limit of detection is unlikely to limit the usefulness of the assay since neuroactive steroid levels in the physiological range are reliably detected, but substantial decreases in neuroactive steroid levels may not be quantifiable.…”

Section: Discussionsupporting

confidence: 76%

“…Although several GC-MS methods are available for measurements of neuroactive steroids[21,22,29,47-51] (see also Purdy et al[52] for review), this is the first demonstration and validation of procedures that allow the simultaneous measurement of eight GABAergic neuroactive steroids and one precursor from the same sample. The method employs highly sensitive negative chemical ionization GC-MS and allows the identification of different isomers (both 5α- and 5β-reduced neuroactive steroids).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, antibodies currently available do not always discriminate among the different isomers of the same compound and this limitation appears to be particularly important in the case of human studies. Humans synthesize both 3α,5α- and 3α,5β-reduced neuroactive steroids[22,44-47]. Considering the abundance of precursors and the common metabolic enzymes, it is likely that the GABAergic metabolites of progesterone, deoxycorticosterone, DHEA and testosterone are both singularly and coordinately significant physiological regulators of central nervous system excitability (see special issue on neuroactive steroids[7]).…”

Section: Introductionmentioning

confidence: 99%

“…Studies using gas chromatography and mass spectrometry (GC-MS) detection of neuroactive steroids have appeared, but are restricted to a few of the GABAergic steroids[21,22,29,47-51] (see also Purdy et al[52] for review). GC-MS allows the simultaneous detection of low amounts of neuroactive steroids in brain, cerebrospinal fluid or serum samples.…”

Section: Introductionmentioning

confidence: 99%

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Simultaneous quantification of GABAergic 3α,5α/3α,5β neuroactive steroids in human and rat serum

et al. 2009

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The 3α,5α-and 3α,5β-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 (3α,5α)-3-hydroxypregnan-20-one (3α,5α-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 3α,5α-and 3α,5β-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 3α,5α-and 3α,5β-reduced neuroactive steroids, indicating differential regulation of their biosynthetic pathways. Pregnenolone administration increased serum levels of 3α,5α-THP (+1488%, p<0.001), (3α,5α)-3,21-dihydroxypregnan-20-one (3α,5α-THDOC, +205%, p<0.01), (3α,5α)-3-hydroxyandrostan-17-one (3α,5α-A, +216%, p<0.001), (3α,5α,17β)-androstane-3,17-diol (3α,5α-A-diol, +190%, p<0.01). (3α,5β)-3-hydroxypregnan-20-one (3α,5β-THP) and (3α,5β)-3-hydroxyandrostan-17-one (3α,5β-A) were not altered, while (3α,5β)-3,21-dihydroxypregnan-20-one (3α,5β-THDOC) and (3α,5β,17β)-androstane-3,17-diol (3α,5β-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 3α,5α-THP (+1806%, p<0.0001), 3α,5β-THP (+575%, p<0.001), 3α,5α-THDOC (+309%, p<0.001). 3α,5β-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 3α,5α-A, 3α,5β-A and pregnenolone were not altered. This method can be used Corresponding Author: A. Leslie Morrow, Ph.D., University of North Carolina School of Medicine, 3027 Thurston-Bowles Building, CB#7178, Chapel Hill, NC, 27599-7178, USA, Tel.: +1-919-9667682, Fax: +1-919-9669099, morrow@med.unc.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptSteroids. Author manuscript; available in PMC 2010 April 1.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Simultaneous quantification of GABAergic 3α,5α/3α,5β neuroactive steroids in human and rat serum

et al. 2009

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Current literature in mass spectrometry

2008

J. Mass Spectrom.

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In order to keep subscribers up‐to‐date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of mass spectrometry. Each bibliography is divided into 11 sections: 1 Reviews; 2 Instrumental Techniques & Methods; 3 Gas Phase Ion Chemistry; 4 Biology/Biochemistry: Amino Acids, Peptides & Proteins; Carbohydrates; Lipids; Nucleic Acids; 5 Pharmacology/Toxicology; 6 Natural Products; 7 Analysis of Organic Compounds; 8 Analysis of Inorganics/Organometallics; 9 Surface Analysis; 10 Environmental Analysis; 11 Elemental Analysis. Within each section, articles are listed in alphabetical order with respect to author (4 Weeks journals ‐ Search completed at 27th. Feb. 2008)

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Neurosteroids and translocator protein 18 kDa (TSPO) ligands as novel treatment options in depression

Riebel,

Brunner,

Nothdurfter

et al. 2024

Eur Arch Psychiatry Clin Neurosci

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Recently, the gamma-aminobutyric acid (GABA) system has come into focus for the treatment of anxiety, postpartum depression, and major depressive disorder. Endogenous 3α-reduced steroids such as allopregnanolone are potent positive allosteric modulators of GABAA receptors and have been known for decades. Current industry developments and first approvals by the U.S. food and drug administration (FDA) for the treatment of postpartum depression with exogenous analogues of these steroids represent a major step forward in the field. 3α-reduced steroids target both synaptic and extrasynaptic GABAA receptors, unlike benzodiazepines, which bind to synaptic receptors. The first FDA-approved 3α-reduced steroid for postpartum depression is brexanolone, an intravenous formulation of allopregnanolone. It has been shown to provide rapid relief of depressive symptoms. An orally available 3α-reduced steroid is zuranolone, which also received FDA approval in 2023 for the treatment of postpartum depression. Although a number of studies have been conducted, the efficacy data were not sufficient to achieve approval of zuranolone in major depressive disorder by the FDA in 2023. The most prominent side effects of these 3α-reduced steroids are somnolence, dizziness and headache. In addition to the issue of efficacy, it should be noted that current data limit the use of these compounds to two weeks. An alternative to exogenous 3α-reduced steroids may be the use of substances that induce endogenous neurosteroidogenesis, such as the translocator protein 18 kDa (TSPO) ligand etifoxine. TSPO has been extensively studied for its role in steroidogenesis, in addition to other functions such as anti-inflammatory and neuroregenerative properties. Currently, etifoxine is the only clinically available TSPO ligand in France for the treatment of anxiety disorders. Studies are underway to evaluate its antidepressant potential. Hopefully, neurosteroid research will lead to the development of fast-acting antidepressants.

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The identification and simultaneous quantification of neuroactive androstane steroids and their polar conjugates in the serum of adult men, using gas chromatography–mass spectrometry

Cited by 10 publications

References 48 publications

Simultaneous quantification of GABAergic 3α,5α/3α,5β neuroactive steroids in human and rat serum

Simultaneous quantification of GABAergic 3α,5α/3α,5β neuroactive steroids in human and rat serum

Current literature in mass spectrometry

Neurosteroids and translocator protein 18 kDa (TSPO) ligands as novel treatment options in depression

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