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E Kitraki

Publications and source records attributed to E Kitraki.

16 recordsLinked to original sources
PubMed2000

Contribution of sex and cellular context in the regulation of brain corticosteroid receptors following restraint stress.

The two subtypes of corticosterone receptors in the rat brain play a pivotal role in the modulation of the stress response. Appropriate control of their gene expression is therefore critical for the maintenance of cellular and organism homeostasis. In this study, we investigated the contribution of gender and of the cellular environment of certain brain areas to the expression of both types of corticosteroid receptors, following restraint stress. Adult Wistar rats of both sexes were subjected to acute, chronic or to a combined chronic plus acute stress regimen, and the expression of glucocorticoid and mineralocorticoid receptors was evaluated in their hippocampus, hypothalamus, pituitary and frontal cortex, by using Northern blot analysis. Significant sex differences were observed in the first three brain areas examined as to the stress-induced expression of corticosteroid receptors. Among these, females showed a distinct mechanism of regulating glucocorticoid/mineralocorticoid receptor ratio in the hippocampus upon chronic stress, while the female hypothalamus was more prone than the male to changing corticosteroid receptor expression in response to restraint stress. In another set of experiments, we assessed the influence of ovarian steroids on stress-induced corticosteroid receptor expression in the above brain areas by analyzing ovariectomized rats exposed to short-term restraint. Our results showed that although ovarian steroids affect the stress-induced expression of receptor genes in a region-specific manner, their elimination does not appear to lead to the male pattern of expression. These findings provide further evidence for the existence of both regional and gender specificity in the regulation of brain and pituitary corticosteroid receptors following stress, and support the hypothesis of a distinct male and female neuroendocrine axis in response to stress.

Adrenal Glands↗
PubMed1999

Neurotransmitter modulation of glucocorticoid receptor mRNA levels in the rat hippocampus.

Glucocorticoids in the hippocampus mediate adaptive responses elicited by stressful stimuli. In this study we investigated glucocorticoid receptor gene expression in the rat hippocampus following acute stress. A significant decrease in glucocorticoid receptor mRNA levels was observed in the hippocampus less than 1 h after the onset of stress. This decrease was inhibited by administering either MK-801, diazepam or propranolol prior to exposure to stress. The effect of diazepam on the stress-induced decrease in hippocampal glucocorticoid receptor mRNA was reversed by Ro-15-1788, suggesting that it is mediated by central benzodiazepine receptors, i.e. GABA-A. These results indicate that NMDA, GABA-A and beta-adrenergic receptors are involved in the mechanism of the stress-induced decrease in glucocorticoid receptor mRNA levels in the rat hippocampus.

Adrenergic beta-Antagonists↗
PubMed1999

Long-lasting effects of stress on glucocorticoid receptor gene expression in the rat brain.

Stressful stimuli are known to affect glucocorticoid receptor (GR) mRNA levels in the rat brain. The aim of this study was to examine the duration of chronic stress-induced changes in GR gene expression in the male rat hippocampus and cerebellum. By using in situ hybridization histochemistry, we detected a statistically significant down-regulation of GR mRNA both in the hippocampus and in the cerebellum of rats stressed for 8, 10 and 14 days. The same degree of down-regulation could also be detected in the above brain areas of rats stressed for 14 days and left undisturbed for 48 h or 8 days after stress. To examine the effects of subsequent stressors on the expression of down-regulated GR mRNA in the hippocampus of chronically stressed rats, we determined, by Northern blotting, GR mRNA levels in the hippocampi of rats stressed for 14 days and subsequently exposed to either short- or long-duration stressors. The down-regulated levels of GR mRNA remained practically unaffected when a subsequent new stressor was applied. Our results show that chronic stress-induced down-regulation of GR mRNA in the rat brain can be extended for periods longer than the initial/causative stimulus, irrespective of the presence of a novel stimulus.

Animals↗
PubMed1998

Beta-adrenergic receptors mediate a stress-induced decrease in IGF-II mRNA in the rat cerebellum.

1. Exposure to a combined forced swimming-confinement stress resulted in a decrease in insulin-like growth factor II (IGF-II) mRNA levels in the whole brain (without the cerebellum) and in the isolated brain areas of the cerebral cortex, the hippocampus, and the cerebellum. 2. In an effort to elucidate the neurotransmitter systems involved in this stress-induced decrease, animals were injected prior to exposure to the stress, with either propranolol, diazepam, or MK-801. 3. Administration of diazepam or MK-801 did not affect the stress-induced decrease in IGF-II mRNA in any of the three brain areas examined. 4. Administration of propranolol prior to the exposure to the stress inhibited the stress-induced decrease in IGF-II mRNA in the cerebellum. Propranolol had no such effect in the cerebral cortex or the hippocampus. 5. Our results suggest that in the cerebellum, the stress-induced decrease in IGF-II mRNA is mediated by beta 2-adrenergic receptors.

Adrenal Cortex Hormones↗
PubMed1997

Glucocorticoid receptor gene expression during rat embryogenesis. An in situ hybridization study.

Glucocorticoids play an important role in embryonic development. The existence of sufficient amounts of their receptors during rodent embryogenesis has proved to be an absolute necessity for the physiological growth of the animal. We have analyzed the pattern of glucocorticoid receptor gene expression in the rat embryo through embryonic days 12 to 17, by using in situ hybridization histochemistry. Glucocorticoid receptor mRNA is present in the rat liver on embryonic day (E) 12, and by E13 the signal can also be detected in several other tissues, such as the lung, the heart, the mesonephros, the sclerotomes, the thymus and Rathke's pouch. Glucocorticoid receptor gene expression was quite ubiquitous in tissue derivatives of all three germ layers and appeared to vary in intensity within the same tissue during embryogenesis. These variations in the level of receptor gene expression paralleled the developmental stage of each tissue: Intense labelling was detected just prior to the final differentiation step of a structure. Upon differentiation, cell populations highly expressing glucocorticoid receptor gene in the previous stage were found to have reduced amounts of the receptor mRNA. Our results support a morphogenetic role for glucocorticoids during embryogenesis.

Animals↗
PubMed1996

Glucocorticoid receptor gene expression in the embryonic rat brain.

The early ontogenetic pattern of glucocorticoid receptor (GR) gene expression was studied in the rat brain through embryonic days (E) 12 to 17. Using a [35S]-labelled GR antisense RNA probe for in situ hybridization, we first detected GR mRNA in E13 embryos. The strongest signal was in Rathke's pouch, but the hypothalamic, and to a lesser degree the pontine and rhinencephalic neuroepithelium were also moderately labelled. Significant levels of GR mRNA were also detected in the choroid plexus and the epithelia lining the ventricles on E13. Receptor gene expression was further extended by E15 to the neuroepithelium and the differentiating field of several neuronal structure primordia, including the basal ganglia, rhinencephalon, hippocampus, pons and cerebellum. On E17, GR gene expression was in addition detected in the amygdala, subiculum and olfactory bulb and cortex. The integrity of the mRNA transcripts revealed by in situ hybridization was assessed by Northern blot analysis of total RNA from embryonic brain and pituitary. A major approximately 7-kb transcript was detected throughout embryonic development. An adult-like GR protein was shown by immunoblotting analysis to be expressed in brain and pituitary extracts already by E13. Based on our results, we postulate a receptor-mediated regulatory role for glucocorticoids in the embryonic development of the rat brain.

Animals↗
PubMed1995

Glucocorticoid regulation of glycerolphosphate dehydrogenase expression in the developing rat brain.

Glucocorticoid regulation of glycerolphosphate dehydrogenase (GPDH) activity and gene expression in the developing rat brain appears complex throughout the postnatal developmental period and attains the adult pattern after the first month of life. GPDH enzyme activity is higher in the limbic system than in the cerebral cortex of intact young animals. Adrenalectomy of young rats, before the first month of life, does not affect GPDH enzyme activity in the brain areas mentioned above, while in the adult animals it results in a statistically significant decrease in activity. Furthermore, "adult type" glucocorticoid responsivity of GPDH enzyme activity is attained in the developing limbic system earlier--by day 40 of life--than in the cerebral cortex. During the first month of life, GPDH basal mRNA levels are increased in the absence of glucocorticoids, in both the limbic system and the cortex, in contrast to the effect of adrenalectomy in the adults, where GPDH mRNA levels are decreased in the absence of the adrenals. The observed pattern of glucocorticoid regulation of GPDH during development in the rat is discussed in relation to the possible existence of various levels of regulation of GPDH gene and enzyme activity.

Animals↗
PubMed1995

Maternal behavior of dams treated with ACTH during pregnancy.

Experimental female rats were injected with ACTH during the last third of their pregnancy. This treatment resulted in prolongation of gestation and in abnormal development of the young. The number of resorptions, stillbirths, and congenitally malformed pups was increased and those that appeared normal had lower body weights. The experimental treatment also severely affected the ability of the dams to exhibit normal maternal behavior. Significant individual differences were noted in the sensitivity of the dams to the experimental treatment. Cross-fostering experiments revealed that experimental dams exhibited normal maternal behavior towards control foster pups, after an initial delay of 24 h. When experimental pups, born after a prolonged gestation, or delivered by caesarian section after the normal duration of gestation, were given to control mothers, normal maternal behavior was observed, but the survival rate of the young was not increased.

Abnormalities, Drug-Induced↗
PubMed1994

Effects of hyperactivity of the maternal hypothalamic-pituitary-adrenal (HPA) axis during pregnancy on the development of the HPA axis and brain monoamines of the offspring.

Offspring of mothers with adrenal hyperactivity during pregnancy have been reported to have changes in brain monoamines and altered emotional, reactive, sexual and maternal behavior. Since the hypothalamic-pituitary-adrenal (HPA) axis is known to be involved in the expression of such behaviors and is itself under monoaminergic control, we examined the development of the HPA axis and brain monoamines in pups whose mothers had adrenal hyperactivity, reflecting administration of ACTH during the last third of their pregnancy. The adrenals of the experimental animals weighed less and had aberrant morphology. The abnormal histology was more pronounced in the adrenals of the experimental females than of the males, suggesting that females were more vulnerable to the prenatal treatment. In both experimental males and females, basal plasma corticosterone levels were higher compared to the controls, while after exposure to stress, experimental animals attained lower plasma corticosterone levels than the controls. In the brain of the experimental animals, dopaminergic activity appeared to be decreased, while serotonergic activity increased. Our results indicate that the prenatal treatment affected brain development in the offspring and as a consequence programmed the developing HPA axis in such a way as to hyperfunction under basal conditions, leading to its exhaustion and its inability to react properly to stress.

Adrenal Glands↗
PubMed1993

Aging-related changes in IGF-II and c-fos gene expression in the rat brain.

The protein products of growth factor genes such as IGF-II and cellular oncogenes such as c-fos are believed to be necessary for the support of normal neuronal function. Steady-state levels of c-fos and IGF-II mRNA were determined in the brain of young and old rats, using Northern analysis. Both RNAs were found to be decreased in the brain of aged rats. Age-related decrease was detected in the hippocampus, hypothalamus, striatum, cerebral cortex and cerebellum, for IGF-II mRNA, and in the cerebral cortex and cerebellum for c-fos mRNA. Furthermore, changes in the degree and pattern of DNA methylation were noted at both gene loci, in the aged rat brain. Our results could reflect changes at the genomic level possibly related to the process of aging and the accompanying decline in brain function.

Aging↗
PubMed1992

Hormonal control of insulin-like growth factor-II gene expression in the rat liver.

IGF-II in the rat is an embryonic/fetal growth factor. Transcription of its gene falls abruptly in the liver at about 18-20 days postnatally. In an attempt to elucidate the mechanisms controlling this phenomenon, we used Northern analysis to investigate the effect of corticosterone and thyroid hormones (tri-iodothyronine and tetra-iodothyronine) on hepatic IGF-II mRNA levels. The administration of either corticosterone or tri-iodothyronine to 8-day-old pups resulted in a significant decrease in IGF-II mRNA when the animals were examined on day 12 of life. Adrenalectomy, thyroidectomy or adrenalectomy combined with thyroidectomy were, however, without effect. Our results indicate that glucocorticoid and thyroid hormones are not the exclusive regulators of IGF-II gene transcription in the rat liver, but participate in this process, which appears to involve multifactorial interactions.

Animals↗
PubMed1984

Glucocorticoid receptors in developing rat brain and liver.

Dexamethasone receptors were measured by conventional equilibrium steroid binding studies in rat liver and brain cytosol, during late prenatal and postnatal development, Receptor binding could be detected in both cytosol preparations as early as the 17th day of gestation. Receptor levels in the cytosol from intact animals reached adult values by the 1st day after birth in both tissues. Using adrenalectomized animals an increase which reached adult values was observed during the first postnatal week for liver and the second postnatal week for brain. At physiological concentrations of endogenous glucocorticoids depletion of receptor from the cytosol of intact animals was minimal at postnatal day 1 and reached adult levels by day 7. Chromatographic analysis in DEAE-Sephadex A50 minicolumns of unactivated and activated receptor constituents revealed the same pattern as that of adult animals. Glucocorticoid receptor complex from developing liver and brain was shown to be capable of binding to isolated adult liver nuclei after in vitro activation. However full capacity, for nuclear binding was observed in vivo, after injection of inducing doses of [3H]dexamethasone: By the end of the first week after birth adult nuclear binding capacity was observed in experiments in vivo while values peaked during the second week, in both tissues studied.

Animals↗
PubMed1983

The distribution and properties of the glucocorticoid receptor from rat brain and pituitary.

The distribution and properties of cytoplasmic binding sites for the synthetic glucocorticoid dexamethasone and the natural glucocorticoid corticosterone in the brain and the pituitary were studied in detail. Cortisol-17 beta acid, a derivative which does not bind to the glucocorticoid receptor but is a competitor of corticosterone binding to plasma, was used to overcome plasma interference. In vitro competition assays in the presence of excess cortisol acid reveal that dexamethasone is as effective a competitor for [3H]corticosterone binding as corticosterone itself. Scatchard analysis of equilibrium experiments with both steroids, using cytosol from various brain areas and from the pituitary yielded linear plots, suggesting one class of binding sites. The quantitative distribution of the sites follows the pattern: cortex greater than hippocampus greater than or equal to pituitary greater than hypothalamus greater than brain stem white matter. Furthermore, kinetic analysis of corticosterone dissociation showed a first order reaction, thus indicating the presence of one type of receptor in all brain areas examined. Rat brain cytosolic receptors for corticosterone and dexamethasone elute from DEAE-Sephadex A-50 anion exchange columns at 0.3 M NaCl in the presence of stabilizing sodium molybdate and at 0.15 M NaCl and/or in the buffer wash when heat-activated, thus exhibiting the characteristic activation pattern of rat liver cytosolic glucocorticoid receptor. The ratio of the buffer wash to the 0.15 M NaCl form is low for dexamethasone and very high for corticosterone. Receptor complexes from various brain parts showed the same activation pattern. In our experiments, brain corticosterone and dexamethasone receptors stabilized by sodium molybdate are indistinguishable by a number of techniques, thus indicating that it is unnecessary to evoke specific binding sites for each glucocorticoid.

Animals↗