A common polymorphism in the mineralocorticoid receptor modulates stress responsiveness
Identifieur interne : 000292 ( France/Analysis ); précédent : 000291; suivant : 000293A common polymorphism in the mineralocorticoid receptor modulates stress responsiveness
Auteurs : Roel H. Derijk [Pays-Bas] ; Stefan Wust [Allemagne] ; Onno C. Meijer [Pays-Bas] ; Maria-Christina Zennaro [France] ; Ilona S. Federenko [États-Unis] ; Dirk H. Hellhammer [Allemagne] ; Gilberta Giacchetti [Italie] ; Erno Vreugdenhil [Pays-Bas] ; Frans G. Zitman [Pays-Bas] ; E. Ronald De Kloet [Pays-Bas]Source :
- The Journal of clinical endocrinology and metabolism [ 0021-972X ] ; 2006.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
Abstract
Context: Mineralocorticoid receptors (MR) mediate the action of aldosterone on sodium resorption in kidney tubular cells, but in brain they respond to the glucocorticoid cortisol in stress regulation and cognitive processes. Objective: The objective of the study was to investigate the role of the MR gene variant I180V in the neuroendocrine response to a psychosocial stressor and in electrolyte regulation. Design: Associations between the MRI180V and outcome variables in a healthy cohort subjected to psychosocial challenge (Trier Social Stress Test) and in a mild hypertensive cohort exposed to acute salt loading (Weinberger's test) were investigated. In vitro transactivational assays were applied to compare the effects of cortisol and aldosterone on the MRI180V. Results: Carriers of the MR180V allele showed higher saliva (P < 0.01), plasma cortisol (P < 0.01), and heart rate responses (P < 0.05) to the Trier Social Stress Test than noncarriers (MR180I). After 3 d of a normal salt diet and the Weinberger's test, no association was found with urinary sodium excretion, plasma aldosterone, and plasma renin activity or with changes in blood pressure, aldosterone, and renin responses. In vitro testing of the MR180V allele revealed a mild loss of function using cortisol as a ligand, compared with the MR180I allele. Significantly higher doses of cortisol were needed for half-maximal induction on the TAT-1 (P < 0.002), TAT-3 (P < 0.03), or mouse mammary tumor virus (P < 0.02) promoters, whereas maximal induction was not different. These differences were not observed using aldosterone as a ligand. Conclusion: The findings reveal that cortisol and heart rate responses to a psychosocial stressor are enhanced in carriers of the MR180V variant.
Affiliations:
- Allemagne, France, Italie, Pays-Bas, États-Unis
- Californie, Rhénanie-Palatinat, Île-de-France
- Paris, Trèves (Allemagne)
- Université de Trèves
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Derijk</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Division of Medical Pharmacology, Leiden University Medical Center, Leiden University</s1><s2>2300 RA Leiden</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>2300 RA Leiden</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Leiden/Amsterdam Center for Drug Research, Department of Psychiatry, Leiden University Medical Center, Leiden University</s1><s2>2300 RA Leiden</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>2300 RA Leiden</wicri:noRegion></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="03"><s1>Department of Psychobiology, University of Trier</s1><s2>54290 Trier</s2><s3>DEU</s3><sZ>2 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>54290 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></author><author><name sortKey="Meijer, Onno C" sort="Meijer, Onno C" uniqKey="Meijer O" first="Onno C." last="Meijer">Onno C. Meijer</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Division of Medical Pharmacology, Leiden University Medical Center, Leiden University</s1><s2>2300 RA Leiden</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>2300 RA Leiden</wicri:noRegion></affiliation></author><author><name sortKey="Zennaro, Maria Christina" sort="Zennaro, Maria Christina" uniqKey="Zennaro M" first="Maria-Christina" last="Zennaro">Maria-Christina Zennaro</name><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Institut National de la Santé et de la Recherche Médicale, U772, College de France</s1><s2>75231 Paris</s2><s3>FRA</s3><sZ>4 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Federenko, Ilona S" sort="Federenko, Ilona S" uniqKey="Federenko I" first="Ilona S." last="Federenko">Ilona S. Federenko</name><affiliation wicri:level="2"><inist:fA14 i1="05"><s1>Department of Psychology and Social Behavior, University of California, Irvine</s1><s2>Irvine, CA 92697-7085</s2><s3>USA</s3><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Californie</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="03"><s1>Department of Psychobiology, University of Trier</s1><s2>54290 Trier</s2><s3>DEU</s3><sZ>2 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>54290 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></author><author><name sortKey="Giacchetti, Gilberta" sort="Giacchetti, Gilberta" uniqKey="Giacchetti G" first="Gilberta" last="Giacchetti">Gilberta Giacchetti</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Clinica di Endocrinologia, Universita Politecnica delle Marche</s1><s2>60131 Ancona</s2><s3>ITA</s3><sZ>7 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>60131 Ancona</wicri:noRegion></affiliation></author><author><name sortKey="Vreugdenhil, Erno" sort="Vreugdenhil, Erno" uniqKey="Vreugdenhil E" first="Erno" last="Vreugdenhil">Erno Vreugdenhil</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Division of Medical Pharmacology, Leiden University Medical Center, Leiden University</s1><s2>2300 RA Leiden</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>2300 RA Leiden</wicri:noRegion></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="1"><inist:fA14 i1="02"><s1>Leiden/Amsterdam Center for Drug Research, Department of Psychiatry, Leiden University Medical Center, Leiden University</s1><s2>2300 RA Leiden</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>2300 RA Leiden</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="1"><inist:fA14 i1="01"><s1>Division of Medical Pharmacology, Leiden University Medical Center, Leiden University</s1><s2>2300 RA Leiden</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>2300 RA Leiden</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">The Journal of clinical endocrinology and metabolism</title><title level="j" type="abbreviated">J. clin. endocrinol. metab.</title><idno type="ISSN">0021-972X</idno><imprint><date when="2006">2006</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">The Journal of clinical endocrinology and metabolism</title><title level="j" type="abbreviated">J. clin. endocrinol. metab.</title><idno type="ISSN">0021-972X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Biological receptor</term><term>Endocrinology</term><term>Genetic variability</term><term>Genotype</term><term>Mineralocorticoid</term><term>Polymorphism</term><term>Stress</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Minéralocorticoïde</term><term>Polymorphisme</term><term>Variabilité génétique</term><term>Génotype</term><term>Récepteur biologique</term><term>Stress</term><term>Endocrinologie</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Context: Mineralocorticoid receptors (MR) mediate the action of aldosterone on sodium resorption in kidney tubular cells, but in brain they respond to the glucocorticoid cortisol in stress regulation and cognitive processes. Objective: The objective of the study was to investigate the role of the MR gene variant I180V in the neuroendocrine response to a psychosocial stressor and in electrolyte regulation. Design: Associations between the MRI180V and outcome variables in a healthy cohort subjected to psychosocial challenge (Trier Social Stress Test) and in a mild hypertensive cohort exposed to acute salt loading (Weinberger's test) were investigated. In vitro transactivational assays were applied to compare the effects of cortisol and aldosterone on the MRI180V. Results: Carriers of the MR180V allele showed higher saliva (P < 0.01), plasma cortisol (P < 0.01), and heart rate responses (P < 0.05) to the Trier Social Stress Test than noncarriers (MR180I). After 3 d of a normal salt diet and the Weinberger's test, no association was found with urinary sodium excretion, plasma aldosterone, and plasma renin activity or with changes in blood pressure, aldosterone, and renin responses. In vitro testing of the MR180V allele revealed a mild loss of function using cortisol as a ligand, compared with the MR180I allele. Significantly higher doses of cortisol were needed for half-maximal induction on the TAT-1 (P < 0.002), TAT-3 (P < 0.03), or mouse mammary tumor virus (P < 0.02) promoters, whereas maximal induction was not different. These differences were not observed using aldosterone as a ligand. Conclusion: The findings reveal that cortisol and heart rate responses to a psychosocial stressor are enhanced in carriers of the MR180V variant.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>France</li><li>Italie</li><li>Pays-Bas</li><li>États-Unis</li></country><region><li>Californie</li><li>Rhénanie-Palatinat</li><li>Île-de-France</li></region><settlement><li>Paris</li><li>Trèves (Allemagne)</li></settlement><orgName><li>Université de Trèves</li></orgName></list><tree><country name="Pays-Bas"><noRegion><name sortKey="Derijk, Roel H" sort="Derijk, Roel H" uniqKey="Derijk R" first="Roel H." last="Derijk">Roel H. Derijk</name></noRegion><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="Meijer, Onno C" sort="Meijer, Onno C" uniqKey="Meijer O" first="Onno C." last="Meijer">Onno C. Meijer</name><name sortKey="Vreugdenhil, Erno" sort="Vreugdenhil, Erno" uniqKey="Vreugdenhil E" first="Erno" last="Vreugdenhil">Erno Vreugdenhil</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="Wust, Stefan" sort="Wust, Stefan" uniqKey="Wust S" first="Stefan" last="Wust">Stefan Wust</name></region><name sortKey="Hellhammer, Dirk H" sort="Hellhammer, Dirk H" uniqKey="Hellhammer D" first="Dirk H." last="Hellhammer">Dirk H. Hellhammer</name></country><country name="France"><region name="Île-de-France"><name sortKey="Zennaro, Maria Christina" sort="Zennaro, Maria Christina" uniqKey="Zennaro M" first="Maria-Christina" last="Zennaro">Maria-Christina Zennaro</name></region></country><country name="États-Unis"><region name="Californie"><name sortKey="Federenko, Ilona S" sort="Federenko, Ilona S" uniqKey="Federenko I" first="Ilona S." last="Federenko">Ilona S. Federenko</name></region></country><country name="Italie"><noRegion><name sortKey="Giacchetti, Gilberta" sort="Giacchetti, Gilberta" uniqKey="Giacchetti G" first="Gilberta" last="Giacchetti">Gilberta Giacchetti</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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