Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study examined the stress responsiveness of the hypothalamic-pituitary-adrenal axis in relation to the properties of corticosteroid receptors in the brain and pituitary in old (30 months) and young (3 months) male Brown Norway rats. The data demonstrate that circulating ACTH rather than the corticosteroid plasma level was elevated under basal conditions and following stress. Furthermore, a reduction of mineralocorticoid receptor (MR) number in the hippocampus and of glucocorticoid receptor (GR) number in the hypothalamus and the pituitary correspond to increased neuroendocrine responsiveness and negative feedback following stress. The changes in receptor binding do not parallel the changes in the amount of MR and GR mRNA measured with in situ hybridization. This suggests that the processing rather than the receptor gene expression is affected in senescence.
 ...
PMID:Brain corticosteroid receptor gene expression and neuroendocrine dynamics during aging. 165 89

A detailed mapping of glucocorticoid receptor (GR) immunoreactivity (IR) in rat CNS was performed employing a mouse monoclonal antibody against rat liver GR. Subjective comparisons were made between the present results and the available data in the literature. A semiquantitation of GR immunostaining was found necessary and was obtained by microdensitometric and morphometric techniques, which enabled the distinction of neuronal and glial cell populations containing GR IR in various CNS regions. GR IR in the CNS was mainly found in the nuclear compartment. The GR was present in neuronal populations with classical neurotransmitters, especially monoamines and glutamate and with various neuropeptides. The degree of colocalization varied according to the function of the brain area. Functional implications were made in relation to stress sensitivity, mood and nociception/antinociception. The global control of networks by glucocorticoids may allow an optimal integration of different types of circuits. The GR is found already in the fetal rat and the development of GR mRNA and receptor protein was followed during the pre- and postnatal periods. The GR appears to be a major factor in brain maturation and in modulation of stress responses. In aged Brown Norway rat brain GR IR but not mineralocorticoid receptor (MR) IR is reduced in the hippocampal nerve cells. The intensity of GR IR but not the number of nerve cells is altered, indicating a reduced activation of the GR in aging in this rat strain. Overall GR participates in neuronal plasticity from fetal and postnatal life to adult life and aging.
 ...
PMID:Glial and neuronal glucocorticoid receptor immunoreactive cell populations in developing, adult, and aging brain. 782 5

The effect of aging on the hippocampal formation of the male Brown Norway rat was studied by immunohistochemistry and measurements of the immunoreactive hippocampal cells using stereological techniques. The total estimated number of glucocorticoid receptor (GR) immunoreactive neurons of the CA1-CA2 area did not differ in the 3- and the 36-month-old rat. However, the intensity of the GR immunoreactivity was decreased in the aged animals. A gradual decrease of the immunoreactivity for the mineralocorticoid receptor was also observed in the CA1-CA2 area. In the stratum oriens and the stratum radiatum of the CA1-CA2 area the immunoreactivity for basic fibroblast growth factor (bFGF) present in the glia was found to be reduced [20,000 +/- 2100 (n = 6)] in the 36-month-old rat vs the 3-month-old rat [28,500 +/- 4500 (n = 4) (*P = 0.05)]. However, there was no difference in the number of glial fibrillary acidic protein immunoreactive cells of this area in these two age groups. The present findings give evidence that in the Brown Norway rat there is no loss of the neuronal population containing glucocorticoid receptors of the CA1-CA2 area during aging but suggest that aging is characterized by deficits of glially derived growth factors, such as bFGF.
 ...
PMID:Basic fibroblast growth factor and steroid receptors in the aging hippocampus of the brown Norway rat: immunocytochemical analysis in combination with stereology. 795 Sep 68

The effects of chronic stress on the hypothalamic-pituaitary-adrenocortical (HPA) axis were studied in five inbred rat strains, i.e. Brown Norway (BN), Fischer (FIS), Lewis (LEW), Spontaneously Hypertensive (SHR) and Wistar Kyoto (WKY). Previously, these rat strains had been shown to display clear behavioral differences in the forced swimming test that presumably measures depression-like behavior, BN and WKY being more passive than the other strains. Here we test the hypothesis that the differences in behavioral immobility might be associated with an abnormal HPA response to chronic immobilization (IMO) stress. In stressnaive rats under basal conditions (morning) there were no differences among strains in adrenal weight, serum adrenocorticotropin hormone (ACTH) and corticosterone (B) levels, cortictropin-releasing factor (CRF) mRNA in the hypothalamic paraventricular nucleus (PVN) and hippocampal glucocorticoid and mineralocorticoid receptor (GR and MR) mRNA. After chronic IMO, basal serum ACTH levels were increased in LEW, SHR and WKY, but not in BN or FIS rats, whereas basal B levels were increased in BN, FIS, SHR and WKY rats, but not in LEW. The increase in adrenal weight was also strain dependent and correlated negatively with chronic IMO-induced hypercorticosteronemia. These peripheral differences among strains were not observed at central levels. Thus, chronic IMO increased the CRF mRNA content in the PVN, analyzed by in situ hybridization, similarly in all strains. In addition, after chronic IMO no differences were found among strains in hippocampal GR mRNA and RM mRNA contents. Considering data from all strains together, chronic IMO reduced the GR mRNA (50-60%) content in the hippocampal CA1, CA3 and DG areas, and slightly diminished (11-13%) MR mRNA levels in CA1 and CA3 areas. The present results indicate that: (i) chronic IMO down-regulates GR mRNA in the hippocampus and slightly up-regulates CRF mRNA in the hypothalamic PVN similarly in all strains; (ii) after chronic IMO interstrain differences were observed in serum ACTH and B levels as well as adrenal hypertrophy; (iii) some changes are probably located at the adrenal level since changes in serum B level and adrenal weight were not related to changes in ACTH; (iv) in LEW and WKY rats, B hyporesponsiveness to chronic IMO might be linked to low adrenal sensitivity to ACTH, and (v) HPA axis changes induced by the chronic IMO procedure are not related to previously reported data on depressive-like behavior of BN and WKY in the forced swimming test.
 ...
PMID:Hypothalamic-pituitary-adrenal response to chronic stress in five inbred rat strains: differential responses are mainly located at the adrenocortical level. 873 88

Microdensitometrical and stereological techniques were applied to study the effects of aging on the hippocampus of 3-, 6-, 12-, 18-, 24-, 30-, and 36-month-old male Brown Norway rats. Stereological analysis of basic fibroblast growth factor (bFGF) immunoreactive glial cells in the CA1 area showed an age-dependent decrease in the number of cells, starting at 18 months of age. Specific mean gray values of the immunoreactivity for bFGF were reduced in the CA3 area, in the dentate gyrus, and in fields of the CA1 area, starting at 24 months of age. There were no differences between the age groups in the number of glial fibrillary acidic protein or glucocorticoid receptor (GR) immunoreactive cells of the CA1-CA2 areas. However, the intensity of the GR immunoreactivity was decreased in the 18-month-old and older rats. No changes in the immunoreactivity for the mineralocorticoid receptor were observed in the CA1-CA2 areas of any of the age groups. Spontaneous alternation test and reactivity in an open field did not reveal marked differences between the age groups. These findings give evidence that there is a loss of neural GR immunoreactivity, but no loss of GR immunoreactive neurons, in the CA1-CA2 areas of the aged Brown Norway rat. Aging may also be characterized by substantial deficits of glially derived growth factors, such as bFGF in the hippocampus. The changes in immunoreactivities were not correlated to alterations in selected behaviors dependent on normal hippocampal function.
 ...
PMID:Neurochemical changes in the hippocampus of the brown Norway rat during aging. 926 98

Adult male Brown Norway rats were long-term intracerebroventricularly (i.c.v.) infused with antisense oligodeoxynucleotides (18-mer, double endcapped phosphorothioate protected) targeting either mineralocorticoid or glucocorticoid receptor mRNA, or received the respective mixed bases sequence or vehicle. Mineralocorticoid receptor-mixed bases and glucocorticoid receptor-mixed bases oligodeoxynucleotide infusion (1 microg/0.5 microl/h) over a time period of seven days did not alter hippocampal mineralocorticoid receptor and glucocorticoid receptor binding when compared to vehicle treatment. In contrast, i.c.v. administration of mineralocorticoid receptor, as well as glucocorticoid receptor-antisense over the same time period resulted in a significantly reduced binding of mineralocorticoid receptor and glucocorticoid receptor in the hippocampus [mineralocorticoid receptor-antisense group approx. 72% of mineralocorticoid receptor-mixed bases and vehicle groups (100%); glucocorticoid receptor antisense group approx. 77% of glucocorticoid receptor-mixed bases and vehicle]. The specificity of these antisense effects is indicated by the finding that rats treated with mineralocorticoid receptor-antisense did not show any changes in glucocorticoid receptor and vice versa. Animals treated according to this infusion protocol and tested in the Morris water maze for their spatial navigation abilities failed to show significant differences among the groups. These data indicate that a reduction of hippocampal mineralocorticoid receptor or glucocorticoid receptor binding capacity by 20-30% does not interfere with spatial navigation.
 ...
PMID:Downregulation of brain mineralocorticoid and glucocorticoid receptor by antisense oligodeoxynucleotide treatment fails to alter spatial navigation in rats. 985 37

During the dark phase of the diurnal cycle, and during recovery from restraint stress, Brown Norway (BN) rats secrete less corticosterone than Fischer 344 (F344) rats. These strains also display different levels of corticosteroid receptors in the hippocampus, and of plasma transcortin. Because corticosteroid receptors, plasma transcortin and corticosterone secretion are mutually regulated, we examined brain and pituitary mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) expression and some of the parameters modulated by these receptors (i.e. body and thymus weight, fluid intake, plasma transcortin) in BN and F344 rat strains, by comparing the effects of either hormone deprivation by long-term (21 days) adrenalectomy (ADX), or chronic elevation of corticosterone given in drinking fluid to ADX rats. In BN rats, body weight gain and fluid intake were insensitive to corticosterone deprivation, suggesting that MR-related mechanisms are constitutively active in this strain. Body weight (b.w.) gain, plasma transcortin and thymus weight were reduced to a greater extent by chronic corticosterone in BN rats than in F344 rats, possibly as a consequence of higher free, active fraction of plasma corticosterone due to lower plasma transcortin concentrations and/or a greater efficiency of GR-related mechanisms in BN rats. F344 rats displayed twofold higher brain and pituitary MR levels than BN rats, whereas tissue-and strain-specific regulations were observed for GR levels. The differences in MR levels observed between BN and F344 strains cannot completely explain the differences in corticosterone actions, suggesting that strain differences in response to ADX or corticosterone treatment result from variable receptor efficiencies.
 ...
PMID:Strain differences in corticosteroid receptor efficiencies and regulation in Brown Norway and Fischer 344 rats. 1022 80

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.
 ...
PMID:Is the mineralocorticoid receptor in Brown Norway rats constitutively active? 1084 87

Our previous studies suggested that the mineralocorticoid receptor (MR) of Brown Norway (BN) male rats is active independently of the presence of its ligands (i.e. constitutively active), and that glucocorticoid receptor (GR)-mediated mechanisms are more efficient in BN than in Fischer 344 (F344) male rats. Such functional differences in corticosteroid receptors led us to compare the effect of adrenalectomy (ADX) and MR/GR-mediated actions (treatments with deoxycorticosterone, DOC and RU 28362, respectively) on female rats from both strains, and, within the framework of a genetic study, to investigate how these differences were inherited in rats of the first generation (F1) born from the crossbreeding between BN and F344 inbred rats. This study extends our previous hypotheses of a constitutive activation of MR and of a greater efficiency of GR in males to females of the BN strain. In both strains, female rats were less sensitive to ADX and to treatments with DOC or RU 28362 than males. Globally, F1 hybrid BNxF344 rats inherited the functional characteristics of MR and GR of BN rats.
 ...
PMID:Effects of adrenalectomy and of mineralocorticoid receptor/glucocorticoid receptor ligands in female Brown Norway and Fischer 344 rats and f1 hybrids. 1212 95

The aim of this research was to identify the molecular bases of differences in sensitivity to corticosteroid hormones between Brown Norway and Fischer 344 rats. We previously showed an apparent insensitivity to adrenalectomy in Brown Norway rats. Based on our first hypothesis of a different activity/reactivity of the mineralocorticoid signaling pathway between the two rat strains, we sequenced Brown Norway and Fischer 344 mineralocorticoid receptor cDNA and identified a tyrosine to cysteine substitution (Y73C) in the N-terminal part of the Brown Norway mineralocorticoid receptor. As a first step, this substitution gave us a means to distinguish the Brown Norway allele from the Fischer 344 at the mineralocorticoid receptor locus in an F2 population. We showed a strong genetic linkage between the mineralocorticoid receptor genotype and sensitivity to adrenalectomy. A subsequent genome-wide linkage analysis confirmed the involvement of the mineralocorticoid receptor locus and implicated other loci, including one on chromosome 4, which collectively explain a large part of the strain differences in corticosteroid receptor responses. In vitro studies further revealed that the Y73C substitution induces greater transactivation of the mineralocorticoid receptor by aldosterone, and surprisingly by progesterone as well, which could substitute for aldosterone after adrenalectomy in Brown Norway rats. We challenged this hypothesis in vivo and showed that plasma progesterone is higher in Brown Norway male rats and partially compensates for aldosterone after adrenalectomy. This work illustrates the interest of a pluristrategic approach to explore the mineralocorticoid receptor signaling pathway and its implication in the regulation of hydroelectrolytic homeostasis and blood pressure.
 ...
PMID:Gain of function mutation in the mineralocorticoid receptor of the Brown Norway rat. 1525 22


1 2 Next >>