Sex specific associations between common glucocorticoid receptor gène variants and hypothalamus-pituitary-adrenal axis responses to psychosocial stress
Identifieur interne : 001380 ( Main/Exploration ); précédent : 001379; suivant : 001381Sex specific associations between common glucocorticoid receptor gène variants and hypothalamus-pituitary-adrenal axis responses to psychosocial stress
Auteurs : Robert Kumsta [Allemagne] ; Sonja Entringer [Allemagne] ; Jan W. Koper [Pays-Bas] ; Elisabeth F. C. Van Rossum [Pays-Bas] ; Dirk H. Hellhammer [Allemagne] ; Stefan Wüst [Allemagne]Source :
- Biological psychiatry : (1969) [ 0006-3223 ] ; 2007.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
- Adaptation, Physiological (genetics), Adaptation, Psychological, Adrenocorticotropic Hormone (blood), Adrenocorticotropic Hormone (drug effects), Adult, Analysis of Variance, Biological receptor, Contraceptives, Oral (pharmacology), Ethinyl Estradiol (pharmacology), Female, Gene, Genetic Variation, Glucocorticoid, Haplotypes, Humans, Hydrocortisone (metabolism), Hypothalamo-Hypophyseal System (drug effects), Hypothalamo-Hypophyseal System (physiology), Hypothalamohypophysoadrenal axis, Hypothalamus, Linkage Disequilibrium, Male, Pituitary gland, Pituitary-Adrenal System (drug effects), Pituitary-Adrenal System (physiology), Polymorphism, Polymorphism, Genetic, Psychosocial factor, Receptors, Glucocorticoid (genetics), Reference Values, Saliva (metabolism), Sensitivity, Sex Factors, Stress, Stress, Psychological (genetics), Stress, Psychological (metabolism).
- MESH :
- chemical , blood : Adrenocorticotropic Hormone.
- chemical , drug effects : Adrenocorticotropic Hormone.
- drug effects : Hypothalamo-Hypophyseal System, Pituitary-Adrenal System.
- genetics : Adaptation, Physiological, Receptors, Glucocorticoid, Stress, Psychological.
- chemical , metabolism : Hydrocortisone, Saliva, Stress, Psychological.
- chemical , pharmacology : Contraceptives, Oral, Ethinyl Estradiol.
- physiology : Hypothalamo-Hypophyseal System, Pituitary-Adrenal System.
- Adaptation, Psychological, Adult, Analysis of Variance, Female, Genetic Variation, Haplotypes, Humans, Linkage Disequilibrium, Male, Polymorphism, Genetic, Reference Values, Sex Factors.
Abstract
Background: Alterations in glucocorticoid (GC) signaling have been associated with a number of psychiatric disorders. Genetic variation of the glucocorticoid receptor (GR) might be one of the factors underlying susceptibility to stress related disease. Methods: We investigated 206 healthy subjects and assessed associations between four common GR gene (NR3C1) polymorphisms (ER22/23EK, N363S, Sc/l, 9β) and hypothalamic-pituitary-adrenal (HPA) axis responses to psychosocial stress (Trier Social Stress Test, TSST) and glucocorticoid sensitivity measured by a dexamethasone suppression test (DST). Results: Male 9β AG carriers displayed the highest adrenocorticotropic hormone (ACTH) and total cortisol TSST responses (for ACTH: main effect genotype? =.02) whereas male Bc/l GG carriers showed diminished responses. Remarkably, the fic/l GG genotype in women (all using oral contraceptives) was associated with the highest total cortisol TSST responses, resulting in a significant sex by genotype interaction (p = .03). Following the DST, male 9p AG carriers had elevated ACTH levels (sex by genotype interaction p =.03). Conclusions: We observed significant sex specific associations between GR gene polymorphisms and HPA axis responses to psychosocial stress as well as GC sensitivity. These findings support the relevance ofGR gene polymorphisms in HPA axis regulation. Genetic variations of the GR might constitute a risk factor in development of HPA axis related disorders.
Affiliations:
- Allemagne, Pays-Bas
- Hollande-Méridionale, Rhénanie-Palatinat
- Rotterdam, Trèves (Allemagne)
- Université de Trèves
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Le document en format XML
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Koper</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Department of Internal Medicine Erasmus Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Van Rossum, Elisabeth F C" sort="Van Rossum, Elisabeth F C" uniqKey="Van Rossum E" first="Elisabeth F. C." last="Van Rossum">Elisabeth F. C. Van Rossum</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Department of Internal Medicine Erasmus Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Hellhammer, Dirk H" sort="Hellhammer, Dirk H" uniqKey="Hellhammer D" first="Dirk H." last="Hellhammer">Dirk H. Hellhammer</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Department of Psychobiology University of Trier</s1><s2>Trier</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><settlement type="city">Trèves (Allemagne)</settlement><region type="land" nuts="1">Rhénanie-Palatinat</region></placeName><orgName type="university">Université de Trèves</orgName></affiliation></author><author><name sortKey="Wust, Stefan" sort="Wust, Stefan" uniqKey="Wust S" first="Stefan" last="Wüst">Stefan Wüst</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Department of Psychobiology University of Trier</s1><s2>Trier</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><settlement type="city">Trèves (Allemagne)</settlement><region type="land" nuts="1">Rhénanie-Palatinat</region></placeName><orgName type="university">Université de Trèves</orgName></affiliation></author></analytic><series><title level="j" type="main">Biological psychiatry : (1969)</title><title level="j" type="abbreviated">Biol. psychiatry : (1969)</title><idno type="ISSN">0006-3223</idno><imprint><date when="2007">2007</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Biological psychiatry : (1969)</title><title level="j" type="abbreviated">Biol. psychiatry : (1969)</title><idno type="ISSN">0006-3223</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adaptation, Physiological (genetics)</term><term>Adaptation, Psychological</term><term>Adrenocorticotropic Hormone (blood)</term><term>Adrenocorticotropic Hormone (drug effects)</term><term>Adult</term><term>Analysis of Variance</term><term>Biological receptor</term><term>Contraceptives, Oral (pharmacology)</term><term>Ethinyl Estradiol (pharmacology)</term><term>Female</term><term>Gene</term><term>Genetic Variation</term><term>Glucocorticoid</term><term>Haplotypes</term><term>Humans</term><term>Hydrocortisone (metabolism)</term><term>Hypothalamo-Hypophyseal System (drug effects)</term><term>Hypothalamo-Hypophyseal System (physiology)</term><term>Hypothalamohypophysoadrenal axis</term><term>Hypothalamus</term><term>Linkage Disequilibrium</term><term>Male</term><term>Pituitary gland</term><term>Pituitary-Adrenal System (drug effects)</term><term>Pituitary-Adrenal System (physiology)</term><term>Polymorphism</term><term>Polymorphism, Genetic</term><term>Psychosocial factor</term><term>Receptors, Glucocorticoid (genetics)</term><term>Reference Values</term><term>Saliva (metabolism)</term><term>Sensitivity</term><term>Sex Factors</term><term>Stress</term><term>Stress, Psychological (genetics)</term><term>Stress, Psychological (metabolism)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Adrenocorticotropic Hormone</term></keywords><keywords scheme="MESH" type="chemical" qualifier="drug effects" xml:lang="en"><term>Adrenocorticotropic Hormone</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Hypothalamo-Hypophyseal System</term><term>Pituitary-Adrenal System</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Adaptation, Physiological</term><term>Receptors, Glucocorticoid</term><term>Stress, Psychological</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Hydrocortisone</term><term>Saliva</term><term>Stress, Psychological</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Contraceptives, Oral</term><term>Ethinyl Estradiol</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Hypothalamo-Hypophyseal System</term><term>Pituitary-Adrenal System</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adaptation, Psychological</term><term>Adult</term><term>Analysis of Variance</term><term>Female</term><term>Genetic Variation</term><term>Haplotypes</term><term>Humans</term><term>Linkage Disequilibrium</term><term>Male</term><term>Polymorphism, Genetic</term><term>Reference Values</term><term>Sex Factors</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Facteur psychosocial</term><term>Glucocorticoïde</term><term>Gène</term><term>Hypophyse</term><term>Hypothalamus</term><term>Facteur psychosocial</term><term>Polymorphisme</term><term>Récepteur biologique</term><term>Sensibilité</term><term>Stress</term><term>Récepteur biologique</term><term>Polymorphisme</term><term>Glucocorticoïde</term><term>Sensibilité</term><term>Hypophyse</term><term>Système hypothalamohypophysosurrénalien</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Background: Alterations in glucocorticoid (GC) signaling have been associated with a number of psychiatric disorders. Genetic variation of the glucocorticoid receptor (GR) might be one of the factors underlying susceptibility to stress related disease. Methods: We investigated 206 healthy subjects and assessed associations between four common GR gene (NR3C1) polymorphisms (ER22/23EK, N363S, Sc/l, 9β) and hypothalamic-pituitary-adrenal (HPA) axis responses to psychosocial stress (Trier Social Stress Test, TSST) and glucocorticoid sensitivity measured by a dexamethasone suppression test (DST). Results: Male 9β AG carriers displayed the highest adrenocorticotropic hormone (ACTH) and total cortisol TSST responses (for ACTH: main effect genotype? =.02) whereas male Bc/l GG carriers showed diminished responses. Remarkably, the fic/l GG genotype in women (all using oral contraceptives) was associated with the highest total cortisol TSST responses, resulting in a significant sex by genotype interaction (p = .03). Following the DST, male 9p AG carriers had elevated ACTH levels (sex by genotype interaction p =.03). Conclusions: We observed significant sex specific associations between GR gene polymorphisms and HPA axis responses to psychosocial stress as well as GC sensitivity. These findings support the relevance ofGR gene polymorphisms in HPA axis regulation. Genetic variations of the GR might constitute a risk factor in development of HPA axis related disorders.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Pays-Bas</li></country><region><li>Hollande-Méridionale</li><li>Rhénanie-Palatinat</li></region><settlement><li>Rotterdam</li><li>Trèves (Allemagne)</li></settlement><orgName><li>Université de Trèves</li></orgName></list><tree><country name="Allemagne"><region name="Rhénanie-Palatinat"><name sortKey="Kumsta, Robert" sort="Kumsta, Robert" uniqKey="Kumsta R" first="Robert" last="Kumsta">Robert Kumsta</name></region><name sortKey="Entringer, Sonja" sort="Entringer, Sonja" uniqKey="Entringer S" first="Sonja" last="Entringer">Sonja Entringer</name><name sortKey="Hellhammer, Dirk H" sort="Hellhammer, Dirk H" uniqKey="Hellhammer D" first="Dirk H." last="Hellhammer">Dirk H. Hellhammer</name><name sortKey="Wust, Stefan" sort="Wust, Stefan" uniqKey="Wust S" first="Stefan" last="Wüst">Stefan Wüst</name></country><country name="Pays-Bas"><region name="Hollande-Méridionale"><name sortKey="Koper, Jan W" sort="Koper, Jan W" uniqKey="Koper J" first="Jan W." last="Koper">Jan W. Koper</name></region><name sortKey="Van Rossum, Elisabeth F C" sort="Van Rossum, Elisabeth F C" uniqKey="Van Rossum E" first="Elisabeth F. C." last="Van Rossum">Elisabeth F. C. Van Rossum</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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