Functional mineralocorticoid receptor (MR) gene variation influences the cortisol awakening response after dexamethasone
Identifieur interne : 000D30 ( Main/Exploration ); précédent : 000D29; suivant : 000D31Functional mineralocorticoid receptor (MR) gene variation influences the cortisol awakening response after dexamethasone
Auteurs : Nienke Van Leeuwen [Pays-Bas] ; Robert Kumsta [Allemagne, Royaume-Uni] ; Sonja Entringer [Allemagne, États-Unis] ; E. Ronald De Kloet [Pays-Bas] ; Frans G. Zitman [Pays-Bas] ; Roel H. Derijk [Pays-Bas] ; Stefan Wust [Allemagne]Source :
- Psychoneuroendocrinology [ 0306-4530 ] ; 2010.
Descripteurs français
- Pascal (Inist)
English descriptors
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Abstract
Stress causes activation of the hypothalamic-pituitary-adrenal (HPA) axis and results in the secretion of corticosteroids, which facilitate behavioral adaptation and promote the termination of the stress response. These actions exerted by cortisol are mediated by two brain corticosteroid receptor types: the high affinity mineralocorticoid (MR) and the low affinity glucocorticoid receptor (GR). Dexamethasone is a potent GR agonist with affinity to MR. Administration of dexamethasone in the evening results in a significant suppression of the morning cortisol awakening response (CAR). Here we tested the involvement of MR variants in this effect of dexamethasone in 218 young healthy subjects (125 females, all using oral contraceptives). For this purpose we determined two single nucleotide polymorphisms (SNPs) in the MR gene, the previously described MRI180V (rs5522) and the MR-2G/C (rs2070951), which both affect in vitro the transactivational capacity of the MR in response to either cortisol or dexamethasone. Administration of a low dose dexamethasone (0.25 mg) at 2300 h resulted in a significant suppression of the cortisol awakening response (CAR). Both SNPs modulated the suppression of the CAR after dexamethasone significantly and in a sex specific manner. Suppression of the CAR was highest in the female MR-2G/C GG subjects while in male GG subjects the dexamethasone suppression of the CAR was attenuated compared to the MR-2G/C GC and CC groups. For the MRI180V, male AA subjects showed after dexamethasone a higher CAR than AG subjects while this effect was not observed in females. The SNPs had no significant influence on the CAR without prior dexamethasone treatment. The association of the CAR with functional MR gene variants only in dexamethasone treated subjects suggests the involvement of MR in dexamethasone induced suppression of morning cortisol.
Affiliations:
- Allemagne, Pays-Bas, Royaume-Uni, États-Unis
- Bade-Wurtemberg, District de Karlsruhe, Hollande-Méridionale, Rhénanie-Palatinat
- Leyde, Mannheim, Trèves (Allemagne)
- Université de Trèves
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uniqKey="Van Leeuwen N" first="Nienke" last="Van Leeuwen">Nienke Van Leeuwen</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research, Leiden University Medical Center</s1><s2>Leiden</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Kumsta, Robert" sort="Kumsta, Robert" uniqKey="Kumsta R" first="Robert" last="Kumsta">Robert Kumsta</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Department of Theoretical and Clinical Psychobiology, University of Trier</s1><s2>Trier</s2><s3>DEU</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Trier</wicri:noRegion><placeName><settlement type="city">Trèves (Allemagne)</settlement><region type="land" nuts="1">Rhénanie-Palatinat</region></placeName><orgName type="university">Université de Trèves</orgName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London and the School of Psychology, University of Southampton</s1><s3>GBR</s3><sZ>2 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London and the School of Psychology, University of Southampton</wicri:noRegion></affiliation></author><author><name sortKey="Entringer, Sonja" sort="Entringer, Sonja" uniqKey="Entringer S" first="Sonja" last="Entringer">Sonja Entringer</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Department of Theoretical and Clinical Psychobiology, University of Trier</s1><s2>Trier</s2><s3>DEU</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Trier</wicri:noRegion><placeName><settlement type="city">Trèves (Allemagne)</settlement><region type="land" nuts="1">Rhénanie-Palatinat</region></placeName><orgName type="university">Université de Trèves</orgName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Psychiatry & Human Behavior, University of California</s1><s2>Irvine</s2><s3>USA</s3><sZ>3 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Irvine</wicri:noRegion></affiliation></author><author><name sortKey="De Kloet, E Ronald" sort="De Kloet, E Ronald" uniqKey="De Kloet E" first="E. Ronald" last="De Kloet">E. Ronald De Kloet</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research, Leiden University Medical Center</s1><s2>Leiden</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Zitman, Frans G" sort="Zitman, Frans G" uniqKey="Zitman F" first="Frans G." last="Zitman">Frans G. Zitman</name><affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Department of Psychiatry, Leiden University Medical Center</s1><s2>Leiden</s2><s3>NLD</s3><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Derijk, Roel H" sort="Derijk, Roel H" uniqKey="Derijk R" first="Roel H." last="Derijk">Roel H. Derijk</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research, Leiden University Medical Center</s1><s2>Leiden</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Department of Psychiatry, Leiden University Medical Center</s1><s2>Leiden</s2><s3>NLD</s3><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Wust, Stefan" sort="Wust, Stefan" uniqKey="Wust S" first="Stefan" last="Wust">Stefan Wust</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Department of Theoretical and Clinical Psychobiology, University of Trier</s1><s2>Trier</s2><s3>DEU</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Trier</wicri:noRegion><placeName><settlement type="city">Trèves (Allemagne)</settlement><region type="land" nuts="1">Rhénanie-Palatinat</region></placeName><orgName type="university">Université de Trèves</orgName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="06"><s1>Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health</s1><s2>Mannheim</s2><s3>DEU</s3><sZ>7 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Mannheim</settlement></placeName></affiliation></author></analytic><series><title level="j" type="main">Psychoneuroendocrinology</title><title level="j" type="abbreviated">Psychoneuroendocrinology</title><idno type="ISSN">0306-4530</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Psychoneuroendocrinology</title><title level="j" type="abbreviated">Psychoneuroendocrinology</title><idno type="ISSN">0306-4530</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antiinflammatory agent</term><term>Awakening</term><term>Dexamethasone</term><term>Gene</term><term>Genetic variability</term><term>Hydrocortisone</term><term>Hypothalamohypophysoadrenal axis</term><term>Mineralocorticoid receptor</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Récepteur minéralocorticoïde</term><term>Gène</term><term>Hydrocortisone</term><term>Réveil</term><term>Dexaméthasone</term><term>Variabilité génétique</term><term>Système hypothalamohypophysosurrénalien</term><term>Antiinflammatoire</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Stress causes activation of the hypothalamic-pituitary-adrenal (HPA) axis and results in the secretion of corticosteroids, which facilitate behavioral adaptation and promote the termination of the stress response. These actions exerted by cortisol are mediated by two brain corticosteroid receptor types: the high affinity mineralocorticoid (MR) and the low affinity glucocorticoid receptor (GR). Dexamethasone is a potent GR agonist with affinity to MR. Administration of dexamethasone in the evening results in a significant suppression of the morning cortisol awakening response (CAR). Here we tested the involvement of MR variants in this effect of dexamethasone in 218 young healthy subjects (125 females, all using oral contraceptives). For this purpose we determined two single nucleotide polymorphisms (SNPs) in the MR gene, the previously described MRI180V (rs5522) and the MR-2G/C (rs2070951), which both affect in vitro the transactivational capacity of the MR in response to either cortisol or dexamethasone. Administration of a low dose dexamethasone (0.25 mg) at 2300 h resulted in a significant suppression of the cortisol awakening response (CAR). Both SNPs modulated the suppression of the CAR after dexamethasone significantly and in a sex specific manner. Suppression of the CAR was highest in the female MR-2G/C GG subjects while in male GG subjects the dexamethasone suppression of the CAR was attenuated compared to the MR-2G/C GC and CC groups. For the MRI180V, male AA subjects showed after dexamethasone a higher CAR than AG subjects while this effect was not observed in females. The SNPs had no significant influence on the CAR without prior dexamethasone treatment. The association of the CAR with functional MR gene variants only in dexamethasone treated subjects suggests the involvement of MR in dexamethasone induced suppression of morning cortisol.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Pays-Bas</li><li>Royaume-Uni</li><li>États-Unis</li></country><region><li>Bade-Wurtemberg</li><li>District de Karlsruhe</li><li>Hollande-Méridionale</li><li>Rhénanie-Palatinat</li></region><settlement><li>Leyde</li><li>Mannheim</li><li>Trèves (Allemagne)</li></settlement><orgName><li>Université de Trèves</li></orgName></list><tree><country name="Pays-Bas"><region name="Hollande-Méridionale"><name sortKey="Van Leeuwen, Nienke" sort="Van Leeuwen, Nienke" uniqKey="Van Leeuwen N" first="Nienke" last="Van Leeuwen">Nienke Van Leeuwen</name></region><name sortKey="De Kloet, E Ronald" sort="De Kloet, E Ronald" uniqKey="De Kloet E" first="E. Ronald" last="De Kloet">E. Ronald De Kloet</name><name sortKey="Derijk, Roel H" sort="Derijk, Roel H" uniqKey="Derijk R" first="Roel H." last="Derijk">Roel H. Derijk</name><name sortKey="Derijk, Roel H" sort="Derijk, Roel H" uniqKey="Derijk R" first="Roel H." last="Derijk">Roel H. Derijk</name><name sortKey="Zitman, Frans G" sort="Zitman, Frans G" uniqKey="Zitman F" first="Frans G." last="Zitman">Frans G. Zitman</name></country><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="Wust, Stefan" sort="Wust, Stefan" uniqKey="Wust S" first="Stefan" last="Wust">Stefan Wust</name><name sortKey="Wust, Stefan" sort="Wust, Stefan" uniqKey="Wust S" first="Stefan" last="Wust">Stefan Wust</name></country><country name="Royaume-Uni"><noRegion><name sortKey="Kumsta, Robert" sort="Kumsta, Robert" uniqKey="Kumsta R" first="Robert" last="Kumsta">Robert Kumsta</name></noRegion></country><country name="États-Unis"><noRegion><name sortKey="Entringer, Sonja" sort="Entringer, Sonja" uniqKey="Entringer S" first="Sonja" last="Entringer">Sonja Entringer</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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