ArticlePloS one2011
Genetic analysis of the neurosteroid deoxycorticosterone and its relation to alcohol phenotypes: identification of QTLs and downstream gene regulation.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 11 citations in OpenAlex.
- Impact of Genetic Variation on Stress-Related Ethanol Consumption.Alcoholism, clinical and experimental research · 2019Article
- Initial genetic dissection of serum neuroactive steroids following chronic intermittent ethanol across BXD mouse strains.Alcohol (Fayetteville, N.Y.) · 2017Article
- Analyses of differentially expressed genes after exposure to acute stress, acute ethanol, or a combination of both in mice.Alcohol (Fayetteville, N.Y.) · 2017Article
- Self-Confirmation and Ascertainment of the Candidate Genomic Regions of Complex Trait Loci - A None-Experimental Solution.PloS one · 2016Article
- Adrenal steroid hormones and ethanol self-administration in male rhesus macaques.Psychopharmacology · 2014Article
- Divergent neuroactive steroid responses to stress and ethanol in rat and mouse strains: relevance for human studies.Psychopharmacology · 2014Review
- Limitation of number of strains and persistence of false positive loci in QTL mapping using recombinant inbred strains.PloS one · 2014Article
- Genetic variation of the cutaneous HPA axis: an analysis of UVB-induced differential responses.Gene · 2013Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundDeoxycorticosterone (DOC) is an endogenous neurosteroid found in brain and serum, precursor of the GABAergic neuroactive steroid (3α,5α)-3,21-dihydroxypregnan-20-one (tetrahydrodeoxycorticosterone, THDOC) and the glucocorticoid corticosterone. These steroids are elevated following stress or ethanol administration, contribute to ethanol sensitivity, and their elevation is blunted in ethanol dependence. METHODOLOGY/PRINCIPAL
findingsTo systematically define the genetic basis, regulation, and behavioral significance of DOC levels in plasma and cerebral cortex we examined such levels across 47 young adult males from C57BL/6J (B6)×DBA/2J (D2) (BXD) mouse strains for quantitative trait loci (QTL) and bioinformatics analyses of behavior and gene regulation. Mice were injected with saline or 0.075 mg/kg dexamethasone sodium salt at 8:00 am and were sacrificed 6 hours later. DOC levels were measured by radioimmunoassay. Basal cerebral cortical DOC levels ranged between 1.4 and 12.2 ng/g (8.7-fold variation, p<0.0001) with a heritability of ∼0.37. Basal plasma DOC levels ranged between 2.8 and 12.1 ng/ml (4.3-fold variation, p<0.0001) with heritability of ∼0.32. QTLs for basal DOC levels were identified on chromosomes 4 (cerebral cortex) and 14 (plasma). Dexamethasone-induced changes in DOC levels showed a 4.4-fold variation in cerebral cortex and a 4.1-fold variation in plasma, but no QTLs were identified. DOC levels across BXD strains were further shown to be co-regulated with networks of genes linked to neuronal, immune, and endocrine function. DOC levels and its responses to dexamethasone were associated with several behavioral measures of ethanol sensitivity previously determined across the BXD strains by multiple laboratories. CONCLUSIONS/SIGNIFICANCE: Both basal and dexamethasone-suppressed DOC levels are positively correlated with ethanol sensitivity suggesting that the neurosteroid DOC may be a putative biomarker of alcohol phenotypes. DOC levels were also strongly correlated with networks of genes associated with neuronal function, innate immune pathways, and steroid metabolism, likely linked to behavioral phenotypes.
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