Chronic Loss of Glucocorticoids Following Adrenalectomy Down‐regulates the Expression of Glucocorticoid Receptor mRNA in the Rat Forebrain

Hu, Zhong‐Ting; Yuri, Kazunari; Morimoto, Masafumi; Ozawa, Hitoshi; Kawata, Mitsuhiro

doi:10.1111/j.1460-9568.1997.tb01536.x

Cited by 8 publications

(4 citation statements)

References 21 publications

(16 reference statements)

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“…The GR‐ir in the anterior pituitary was unaffected by MTP, which suggests that the regulation of GR expression is cell type dependent and also argues against a nonspecific toxicity of the MTP. In the rat, by contrast to the short‐term (<1 week) effects of ADX (discussed above), 1 week of ADX produced a marked decrease in GR‐ir in several brain areas (Hu et al,1997b; Rosenfeld et al,1988; Visser et al,1996), and longer‐term ADX (≥1 week) resulted in the loss of detectable GR‐ir throughout the brain (Han et al,2005; Hu et al,1997a; Visser et al,1996). Taken together, our findings in the frog and those in the rat suggest that, although elevated GCs can negatively regulate GR expression, a basal GC level may be required for maintaining GR expression over the longer term.…”

Section: Discussionmentioning

confidence: 99%

Distribution and corticosteroid regulation of glucocorticoid receptor in the brain of Xenopus laevis

Yao

Denver

2008

J of Comparative Neurology

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Glucocorticoids (GCs) play essential roles in physiology, development, and behavior that are mediated largely by the glucocorticoid receptor (GR). Although the GR has been intensively studied in mammals, very little is known about the GR in nonmammalian tetrapods. We analyzed the distribution and GC regulation of GR in the brain of the frog Xenopus laevis by immunohistochemistry. GR-immunoreactive (GR-ir) cells were widely distributed, with the highest densities in the medial pallium (mp; homolog of the mammalian hippocampus), accumbens, anterior preoptic area (POA; homolog of the mammalian paraventricular nucleus), Purkinje cell layer of the cerebellum, and rostral anterior pituitary gland (location of corticotropes). Lower but distinct GR-ir was observed in the internal granule cell layer of the olfactory bulbs, dorsal and lateral pallium, striatum, various subfields of the amygdala, bed nucleus of the stria terminalis (BNST), optic tectum, various tegmental nuclei, locus coeruleus, raphe nuclei, reticular nuclei, and the nuclei of the trigeminal motor nerves. Treatment with corticosterone (CORT) for 4 days significantly decreased GR-ir in the POA, mp, medial amygdala (MeA), BNST, and rostral pars distalis. Treatment with the corticosteroid synthesis inhibitor metyrapone (MTP) also significantly reduced GR-ir in the POA, mp, MeA and BNST, but not in the rostral pars distalis. Replacement with a low dose of CORT in MTP-treated animals reversed these effects in brain. Thus, chronic increase or decrease in circulating corticosteroids reduces GR-ir in regions of the frog brain. Our results show that the central distribution of GR-ir and regulation by corticosteroids are highly conserved among vertebrates.

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Section: Discussionmentioning

confidence: 99%

Distribution and corticosteroid regulation of glucocorticoid receptor in the brain of Xenopus laevis

Yao

Denver

2008

J of Comparative Neurology

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“…As with plasma ACTH, the increase of corticosteroid receptors is caused by the removal of the negative control exerted by corticosterone on receptor synthesis ( 65). Tissue‐specific regulation of receptor synthesis after long‐term ADX ( 66) may contribute to the decrease in MRs observed in pituitary and hippocampus, or in GRs in hippocampus, after 14 days of ADX. The region‐specific neuronal loss classically described after long‐term ADX in hippocampus ( 54) could add further to such a regulation of receptor synthesis.…”

Section: Discussionmentioning

confidence: 99%

Is the Mineralocorticoid Receptor in Brown Norway Rats Constitutively Active?

Marissal-Arvy

Ribot

Sarrieau

et al. 2000

J Neuroendocrinology

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In a previous study using corticosterone treatment of adrenalectomized rats, we hypothesized that mineralocorticoid receptor (MR)-related mechanisms are constitutively active and that glucocorticoid receptor (GR)-mediated mechanisms are more efficient in Brown Norway rats compared to Fischer 344 (F344) rats. In order to discriminate the mineralocorticoid from the glucocorticoid actions exerted by corticosterone, F344 and Brown Norway adrenalectomized rats were treated with increasing doses (1, 5 and 25 microg/ml of drinking water) of deoxycorticosterone (DOC, MR-specific ligand) or RU 28362 (GR-specific ligand). These rats were compared with long-term adrenalectomized (ADX) untreated rats and sham-ADX rats. This study confirms our previous results, notably the lack of effect of ADX on body weight and fluid intake in Brown Norway rats. Moreover, DOC treatment had no effect in Brown Norway rats whereas the higher dose restored fluid intake of the F344 ADX group to sham values. These results support the hypothesis of a constitutive activation of the MR and therefore the insensitivity of this receptor to its ligand in Brown Norway rats. Alternatively, RU 28362 treatment induced greater weight loss, decrease in food intake, anxiolysis, thymus involution, and decrease in plasma transcortin concentration and pituitary corticosteroid receptor densities in Brown Norway rats than in F344 rats, which is consistent with greater efficiency of GR mechanisms in Brown Norway rats than in F344 rats. Therefore, these strains are of great utility to disentangle MR and GR effects on complex phenotypes.

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“…In this in vivo model, apoptosis is visible after 3 days in some DG cells while most cells – sharing the same microenvironment – remain intact (Sloviter et al ., 1989). Low concentrations of corticosterone, sufficient to activate high‐affinity mineralocorticoid receptors (MRs) but not lower affinity glucocorticoid receptors (GRs) can fully prevent apoptosis (Woolley et al ., 1991; Sloviter et al ., 1993; Hu et al ., 1997).…”

Section: Introductionmentioning

confidence: 99%

Gene expression profiles associated with survival of individual rat dentate cells after endogenous corticosteroid deprivation

Nair

Karst

Dumas

et al. 2004

Eur J of Neuroscience

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Removal of circulating corticosterone by adrenalectomy (ADX) leads to apoptosis after 3 days in a small population of rat dentate granule neurons, whereas most surrounding cells remain viable. Interestingly, a specific expression profile is triggered in surviving granule cells that may enhance their survival. Hippocampal slices prepared 1, 2 or 3 days after ADX or sham operation were stained ex vivo with Hoechst 33258, which serves to identify apoptotic neurons. After electrophysiological analysis, multiple gene expression in surviving individual granule cells was assessed by linear antisense RNA amplification and hybridization to slot blots containing various neuronal cDNAs. Hierarchical clustering and principal component analysis was performed on two physiological variables and 14 mRNA ratios from ADX cells from every time point. Our results indicate that surviving 3-day ADX granule cells display lower membrane capacitance, lower relative N-methyl-d-aspartate (NMDA) R1 mRNA expression and higher relative mineralocorticoid receptor (MR), alpha1A voltage-gated Ca-channel, Bcl-2 and NMDA R2C mRNA expression. Some 1- and 2-day ADX cells cluster with these 3-day survivors; therefore, one or more components of their mRNA expression profile may represent predictive markers for apoptosis resistance. The functional relevance of two candidate genes was tested by in vivo local over-expression in the same model system; of these, Bcl-2 conferred partial protection when induced shortly before ADX. Therefore, removal of corticosteroids triggers a specific gene expression profile in surviving dentate granule cells; key components of this profile may be associated with their survival.

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Chronic Loss of Glucocorticoids Following Adrenalectomy Down‐regulates the Expression of Glucocorticoid Receptor mRNA in the Rat Forebrain

Cited by 8 publications

References 21 publications

Distribution and corticosteroid regulation of glucocorticoid receptor in the brain of Xenopus laevis

Distribution and corticosteroid regulation of glucocorticoid receptor in the brain of Xenopus laevis

Is the Mineralocorticoid Receptor in Brown Norway Rats Constitutively Active?

Gene expression profiles associated with survival of individual rat dentate cells after endogenous corticosteroid deprivation

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