Autoregulation of glucocorticoid receptor gene expression

Burnstein, Kerry L.; Bellingham, Deborah L.; Jewell, Christine M.; Powell-Oliver, Frances E.; Cidlowski, John A.

doi:10.1016/0039-128x(91)90124-e

Cited by 146 publications

(101 citation statements)

References 35 publications

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“…A monophasic rhythm of both transcripts was seen, with the data fitting better with other diurnal processes (and the corticosterone rhythm) than the biphasic rhythm of MR reported previously by Herman et al (1993). GR mRNA was clearly suppressed by the continuously if very modestly elevated corticosterone levels with fixed-replacement, suggesting sensitive autoregulation (Burnstein et al, 1991). In food-restricted rats, however, there was clear divergence from the expected inverse relationship between corticosterone levels and GR gene expression, with overall hypersecretion of corticosterone associated with increased GR mRNA in CA1 at some time points and maintained expression at all others.…”

Section: Gr and Mr Rhythmssupporting

confidence: 78%

Dysregulation of Diurnal Rhythms of Serotonin 5-HT_2Cand Corticosteroid Receptor Gene Expression in the Hippocampus with Food Restriction and Glucocorticoids

Holmes

French

1997

J. Neurosci.

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Both serotonergic dysfunction and glucocorticoid hypersecretion are implicated in affective and eating disorders. The adverse effects of serotonergic (5-HT) 2C receptor activation on mood and food intake, the antidepressant efficacy of 5-HT 2 receptor antagonists, and the hyperphagia observed in 5-HT 2C receptor knockout mice all suggest a key role for increased 5-HT 2C receptor-mediated neurotransmission. Glucocorticoids, however, downregulate 5-HT 2C receptor mRNA in the hippocampus, and it is unclear how increased 5-HT 2C receptor sensitivity is achieved in the presence of elevated glucocorticoid levels in depression. Here we show a monophasic diurnal rhythm of 5-HT 2C receptor mRNA expression in the rat hippocampus that parallels time-dependent variations in 5-HT 2C receptor agonist-induced behaviors in open field tests. Rats entrained to chronic food restriction show marked but intermittent corticosterone hypersecretion and maintain an unaltered 5-HT 2C receptor mRNA rhythm. The 5-HT 2C receptor mRNA rhythm, however, is suppressed by even modest constant elevations of corticosterone (adrenalectomy ϩ pellet) or with elevated corticosterone during the daytime (8 A.M.), whereas a normal rhythm exists in animals that have the same dose of corticosterone in the evening (6 P.M.). Thus, animals showing even a transient daytime corticosterone nadir exhibit normal hippocampal 5-HT 2C receptor mRNA rhythms, even in the presence of overt corticosterone hypersecretion. Chronic food restriction also abolishes the normal diurnal variation in hippocampal glucocorticoid receptor (GR) and mineralocorticoid receptor mRNAs and produces, unusually, both elevated corticosterone and increased GR. The mismatch between elevated glucocorticoids and maintained 5-HT 2C receptor and increased GR gene expression in the hippocampus provides a new model to dissect mechanisms that may underlie affective and eating disorders.

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Section: Gr and Mr Rhythmssupporting

confidence: 78%

Dysregulation of Diurnal Rhythms of Serotonin 5-HT_2Cand Corticosteroid Receptor Gene Expression in the Hippocampus with Food Restriction and Glucocorticoids

Holmes

French

1997

J. Neurosci.

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“…Such lowered stress reactivity may result from alterations in tissue sensitivity to stress hormones (Bamberger et al, 1996;Wirtz et al, 2003). For example, excess stress hormone availability can lead to regulatory receptor downregulation in order to keep homeostasis of the interior milieu (Lefkowitz et al, 1984;Burnstein et al, 1991;Wirtz, 2002). A contrary mechanism however could be that tissue sensitivity is enhanced leading to compensatory down-regulation of hormone production.…”

Section: Discussionmentioning

confidence: 99%

Higher overcommitment to work is associated with lower norepinephrine secretion before and after acute psychosocial stress in men

Wirtz

Siegrist

Rimmele

et al. 2008

Psychoneuroendocrinology

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Higher overcommitment to work is associated with lower norepinephrine secretion before and after acute psychosocial stress in men Higher overcommitment to work is associated with lower norepinephrine secretion before and after acute psychosocial stress in men Abstract BACKGROUND: Overcommitment (OC) is a pattern of excessive striving. In reaction to work stress, OC has been associated with higher sympathetic nervous system activation and cortisol release, but data on neuroendocrine reactivity to standardized stressors are scarce. We investigated whether OC is associated with differential levels of the stress hormones norepinephrine and cortisol in response to acute psychosocial stress.METHODS: Fifty-eight medication-free non-smoking men aged between 20 and 65 years (mean+/-S.E.M.: 36.3+/-1.8) underwent an acute standardized psychosocial stress task combining public speaking and mental arithmetic in front of an audience. We assessed OC as well as a variety of psychological control variables including vital exhaustion, perfectionism, chronic stress, and cognitive stress appraisal. Moreover, we measured plasma norepinephrine as well as salivary cortisol before and after stress and several times up to 60 min thereafter.RESULTS: Higher OC was associated with lower baseline norepinephrine levels (r = -0.37, p < 0.01). General linear models controlling for age, BMI, and mean arterial blood pressure revealed that higher overcommitment was associated with lower norepinephrine and cortisol levels before and after stress (p's < 0.02) as well as with lower norepinephrine stress reactivity (p = 0.02). Additional controlling for the potential psychological confounders vital exhaustion, perfectionism, chronic stress, and depression confirmed lower norepinephrine levels before and after stress (p < 0.01) as well lower norepinephrine stress reactivity (p = 0.02) with increasing OC. Higher OC independently explained 13% of the total norepinephrine stress response (beta = -0.46, p < 0.01, R(2) change = 0.13).CONCLUSIONS: Our findings suggest blunted increases in norepinephrine following stress with increasing OC potentially mirroring blunted stress reactivity of the sympathetic nervous system. ABSTRACTBackground: Overcommitment is a pattern of excessive striving. In reaction to work stress, overcommitment (OC) has been associated with higher sympathetic nervous system activation and cortisol release, but data on neuroendocrine reactivity to standardized stressors are scarce. We investigated whether overcommitment is associated with differential levels of the stress hormones norepinephrine and cortisol in response to acute psychosocial stress.Methods: 58 medication-free non-smoking men aged between 20 and 65 years (mean±SEM: 36.3±1.8) underwent an acute standardized psychosocial stress task combining public speaking and mental arithmetic in front of an audience. We assessed overcommitment as well as a variety of psychological control variables including vital exhaustion, perfectionism, chronic stress, and cognitive stress appraisa...

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“…Indeed, adipose tissue produces excess glucocorticoids (Pasquali et al, 2006), which in turn could down-regulate GC receptor expression (Burnstein et al, 1991). However, as BMI was not related to altered cortisol stress reactivity, it is unlikely that the stress-induced changes in GC sensitivity are due to excess cortisol secretion following stress.…”

Section: Discussionmentioning

confidence: 99%

Higher body mass index (BMI) is associated with reduced glucocorticoid inhibition of inflammatory cytokine production following acute psychosocial stress in men

Wirtz

Ehlert

Emini

et al. 2008

Psychoneuroendocrinology

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Autoregulation of glucocorticoid receptor gene expression

Cited by 146 publications

References 35 publications

Dysregulation of Diurnal Rhythms of Serotonin 5-HT_2Cand Corticosteroid Receptor Gene Expression in the Hippocampus with Food Restriction and Glucocorticoids

Dysregulation of Diurnal Rhythms of Serotonin 5-HT_2Cand Corticosteroid Receptor Gene Expression in the Hippocampus with Food Restriction and Glucocorticoids

Higher overcommitment to work is associated with lower norepinephrine secretion before and after acute psychosocial stress in men

Higher body mass index (BMI) is associated with reduced glucocorticoid inhibition of inflammatory cytokine production following acute psychosocial stress in men

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Autoregulation of glucocorticoid receptor gene expression

Cited by 146 publications

References 35 publications

Dysregulation of Diurnal Rhythms of Serotonin 5-HT2Cand Corticosteroid Receptor Gene Expression in the Hippocampus with Food Restriction and Glucocorticoids

Dysregulation of Diurnal Rhythms of Serotonin 5-HT2Cand Corticosteroid Receptor Gene Expression in the Hippocampus with Food Restriction and Glucocorticoids

Higher overcommitment to work is associated with lower norepinephrine secretion before and after acute psychosocial stress in men

Higher body mass index (BMI) is associated with reduced glucocorticoid inhibition of inflammatory cytokine production following acute psychosocial stress in men

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Dysregulation of Diurnal Rhythms of Serotonin 5-HT_2Cand Corticosteroid Receptor Gene Expression in the Hippocampus with Food Restriction and Glucocorticoids

Dysregulation of Diurnal Rhythms of Serotonin 5-HT_2Cand Corticosteroid Receptor Gene Expression in the Hippocampus with Food Restriction and Glucocorticoids