Development of mRNAs for glucocorticoid and mineralocorticoid receptors in rat hippocampus

Bohn, Martha C.; Dean, Deyrick; Hussain, Safdar; Giuliano, Rita

doi:10.1016/0165-3806(94)90192-9

Cited by 61 publications

(35 citation statements)

References 48 publications

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“…Also in contrast to GR mRNA expression, MR mRNA expression was very low or absent until the last 3 d of gestation, when it became more prominent in the hippocampus and lateral septum. Indeed, at the end of gestation, MR was higher than GR mRNA expression in the hippocampus and septum, confirming previous observations (Bohn et al, 1994). MR binding sites have been reported in both neurons and glia in fetal hippocampal cell cultures (Bohn et al, 1991), suggesting that MR mRNA is likely to be translated.…”

Section: Gr and Mr Expression In Fetal Brainsupporting

confidence: 77%

Distinct Ontogeny of Glucocorticoid and Mineralocorticoid Receptor and 11β-Hydroxysteroid Dehydrogenase Types I and II mRNAs in the Fetal Rat Brain Suggest a Complex Control of Glucocorticoid Actions

1998

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Glucocorticoids (GCs) act via intracellular mineralocorticoid (MR) and glucocorticoid receptors (GR). However, it has recently been recognized that GC access to receptors is determined by the presence of tissue-specific 11β-hydroxysteroid dehydrogenases (11β-HSDs) that catalyze the interconversion of active corticosterone and inert 11-dehydrocorticosterone. 11β-HSD type 1 (11β-HSD1) is a bidirectional enzymein vitrothat acts predominantly as a reductase (regenerating corticosterone) in intact neurons. In contrast, 11β-HSD type 2 (11β-HSD2) is a higher affinity exclusive dehydrogenase that excludes GCs from MR in the kidney, producing aldosterone-selectivityin vivo. We have examined the ontogeny of 11β-HSD mRNAs and enzyme activity during prenatal brain development and correlated this with GR and MR mRNA development. These data reveal that (1) 11β-HSD2 mRNA is highly expressed in all CNS regions during midgestation, but expression is dramatically reduced during the third trimester except in the thalamus and cerebellum; (2) 11β-HSD2-like activity parallels closely the pattern of mRNA expression; (3) 11β-HSD1 mRNA is absent from the CNS until the the third trimester, and activity is low or undectectable; and (4) GR mRNA is highly expressed throughout the brain from midgestation, but MR gene expression is absent until the last few days of gestation. High 11β-HSD2 at midgestation may protect the developing brain from activation of GR by GCs. Late in gestation, repression of 11β-HSD2 gene expression may allow increasing GC activation of GR and MR, permitting key GC-dependent neuronal and glial maturational events.

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Section: Gr and Mr Expression In Fetal Brainsupporting

confidence: 77%

Distinct Ontogeny of Glucocorticoid and Mineralocorticoid Receptor and 11β-Hydroxysteroid Dehydrogenase Types I and II mRNAs in the Fetal Rat Brain Suggest a Complex Control of Glucocorticoid Actions

1998

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“…Previous developmental studies have shown that MR and GR gene transcripts are detectable in brain during neonatal life. Their level remains relatively constant between post-natal days 5 and 15, sub sequently higher adult levels are reached at day 30 [3,22], The present study is generally in support of this age-depen dent change. However, in some discrete brain regions critical for neuroendocrine regulation, the developmental receptor mRNA pattern between the two rat lines is differ ent.…”

Section: Ny Rots Et Al/ Developmental Bruiti Research 92 (1996) ì6supporting

confidence: 74%

“…Sex differences in MR and GR as well as TH mRNA expression only start to occur after post-natal day 25 [2,3]. Moreover, there are no sex differences between apo-sus and apo-unsus rats in the gnawing response [5].…”

Section: Ny Rots Et Al/ Developmental Bruiti Research 92 (1996) ì6mentioning

confidence: 99%

Development of divergence in dopamine responsiveness in genetically selected rat lines is preceded by changes in pituitary-adrenal activity

Rots

Workel²,

Oitzl³

et al. 1996

Developmental Brain Research

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A b s tra c tTwo pharmacogenetically selected Wistar rat lines have been used as a model for individual variability in behavioral and neuroendocrine responses. As a selection criterion the behavioral responsiveness For the dopamine agonist apomorphine was used, giving rise to the apomorphine-susceptible (apo-sus) and apomorphine-unsuseeptible (apo-unsus) rat lines. This selection has been maintained over 16 generations. Recent studies have shown that adult rats of these selection lines also show pronounced differences in responsiveness of the hypothalamic-pituitary-adrenal (HPA) system. In this study we analyzed to what extent the divergence in dopamine phenotype and HPA responsiveness, as observed in adult rats, are linked to possible differences, within both systems, during early postnatal development. Therefore, we measured in neonatal female rats of 10 and 18 days of age several parameters of the dopamine and UFA system which show significant differences in adult rats. These include tyrosine hydroxylase (TH) and dopamine D1 and D2 receptor mRNA levels, which were determined within the nigrostriatal system since this system shows the most pronounced differences hot ween adult rats oF both selection lines. As indices of HPA activity we measured CRH mRNA, ACTH and total and free corticosterone plasma concentrations under basal conditions in the morning. Transcripts of the two types of corticosteroid receptors, mineralocorticoid (MR) and glucocorticoid (GR) receptor were measured in hippocampus and paraventricular nucleus. In 10-day-old rats all dopamine and MPA parameters were similar in rats of the two selection lines, except for GR mRNA in the parvocellular neurons of the paraventricular nucleus of the hypothalamus (PVN) of apo-sus rats, which was significantly higher than in apo-unsus rats. Highteeu-day-old apo-sus rats, however, showed significantly higher ACTH, comparable total corticosterone and a trend towards lower Free corticosterone plasma levels. This HPA profile resembles the situation in adult apo-sus rats as compared with adult apo-unsus rats. Hippocampal GR mRNA expression and thymus weight were also higher in apo-sus rats. In addition, these rats showed an age-related increase in hippocampal MR mRNA expression, while in apo-unsus rats M R mRNA levels did not change between pnd 10 and 18. The measures of the nigrostriatal dopfimme system at day 18 were still similar in rats oF both lines. In conclusion, divergence in the dopamine systems of the two pliarmaeogenetieally selected rat lines emerges subsequent to divergence in pituitary-adrenal activity.

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“…55,56 Within the human brain, GR mRNA has been shown to be present in the vast majority of pyramidal neurons, B50% of the non-pyramidal neurons and 10% of the glia in the hippocampus and prefrontal, temporal and entorhinal cortices. 43,57 Across rodent development, consistent increases in hippocampal and cortical GR mRNA 58,59 and cortical, limbic and subcortical GR protein 2 have been shown. Furthermore, changes in abundance of multiple GR protein isoforms across rodent hippocampal development have been described.…”

Section: Introductionmentioning

confidence: 99%

Dynamic molecular and anatomical changes in the glucocorticoid receptor in human cortical development

et al. 2010

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The glucocorticoid receptor (GR) has a critical role in determining the brain's capacity to respond to stress, and has been implicated in the pathogenesis of psychiatric illness. We hypothesized that key changes in cortical GR occur during adolescence and young adulthood, at a time when individuals are at increased risk of developing schizophrenia, bipolar disorder and major depression. We investigated the mRNA and protein expression of GR in the dorsolateral prefrontal cortex across seven developmental time points from infancy to adulthood. GR mRNA expression, determined by microarray and quantitative real-time PCR, was lowest in neonates and peaked around young adulthood. Western blotting revealed two dynamic patterns of GRa protein expression across the lifespan, with N-terminal variants displaying differing unique patterns of abundance. GRa-A and a 67-kDa GRa isoform mirrored mRNA trends and peaked in toddlers and late in adolescence, whereas a 40-kDa isoform, very likely a GRa-D variant, peaked in neonates and decreased across the lifespan. GRa protein was localized to pyramidal neurons throughout life and most strikingly in young adulthood, but to white matter astrocytes only in neonates and infants ( < 130 days). These results suggest that the neonatal and late adolescent periods represent critical windows of stress pathway development, and highlight the importance of white matter astrocytes and pyramidal neurons, respectively, at these stages of cortical development. Evidence of dynamic patterns of GR isoform expression and cellular localization across development strengthens the hypothesis that windows of vulnerability to stress exist across human cortical development.

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Development of mRNAs for glucocorticoid and mineralocorticoid receptors in rat hippocampus

Cited by 61 publications

References 48 publications

Distinct Ontogeny of Glucocorticoid and Mineralocorticoid Receptor and 11β-Hydroxysteroid Dehydrogenase Types I and II mRNAs in the Fetal Rat Brain Suggest a Complex Control of Glucocorticoid Actions

Distinct Ontogeny of Glucocorticoid and Mineralocorticoid Receptor and 11β-Hydroxysteroid Dehydrogenase Types I and II mRNAs in the Fetal Rat Brain Suggest a Complex Control of Glucocorticoid Actions

Development of divergence in dopamine responsiveness in genetically selected rat lines is preceded by changes in pituitary-adrenal activity

Dynamic molecular and anatomical changes in the glucocorticoid receptor in human cortical development

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