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Functional mineralocorticoid receptor (MR) gene variation influences the cortisol awakening response after dexamethasone.

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 (0.25mg) at 2300h 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.

journal_name

Psychoneuroendocrinology

journal_title

Psychoneuroendocrinology

authors

van Leeuwen N,Kumsta R,Entringer S,de Kloet ER,Zitman FG,DeRijk RH,Wüst S

doi

10.1016/j.psyneuen.2009.07.006

subject

Has Abstract

pub_date

2010-04-01 00:00:00

pages

339-49

issue

eissn

0306-4530

issn

1873-3360

pii

S0306-4530(09)00219-4

journal_volume

pub_type

临床试验,杂志文章

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Functional mineralocorticoid receptor (MR) gene variation influences the cortisol awakening response after dexamethasone.