Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of corticosterone injection and of acute and repeated stress on rat liver cytosol glucocorticoid receptor was studied to ascertain whether corticosterone-induced glucocorticoid receptor (GR) regulation also takes place in intact animals as it does in adrenalectomized ones. Adult male rats were exposed to six different stressors (swimming, 10 mg/kg histamine i.p., 500 mU/kg vasopressin s.c., heat, immobilization and cold) acutely or three times daily for 18 days (repeated stress). Each of the stressors applied acutely provoked a pronounced increase of plasma corticosterone with subsequent induction of hepatic tyrosine aminotransferase activity. Depletion of cytosol receptor was however only noticed after swimming and histamine injection. On the other hand, sustained hypersecretion of corticosterone evoked by repeated stress significantly reduced the number of GR in rat liver cytosol without any change in Kd. It is concluded that in the presence of intact adrenal glands cytosol receptors are more resistant to corticosterone-induced depletion than in their absence. Further, repeated stress causes down-regulation of GR in the liver, most probably by sustained corticosterone secretion, yet the effect of other stress factors cannot be excluded.
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PMID:Stress-induced changes of glucocorticoid receptor in rat liver. 161 78

The three major classes of neurons in the paraventricular nucleus (PVH) provide a rich model for studying hormonal and neural influences on multiple neuropeptides expressed in individual cells. A great deal of previous work has examined this problem at the immunohistochemical level, where hormonal and neural influences on peptide levels have been established. In situ hybridization methods were used here to determine whether these effects are accompanied by measurable changes in neuropeptide mRNA levels. In the first series of experiments, the time-course of corticosterone replacement effects on corticotropin-releasing hormone (CRH) mRNA levels in parvicellular neuroendocrine cells of adrenalectomized animals were determined, and a dose-response curve was established. CRH mRNA hybridization remains maximal with plasma levels of steroid up to about 50 ng/ml, then declines sharply between about 60-130 ng/ml, and is just detectable at higher levels. We confirmed that corticosterone decreases vasopressin mRNA levels in this cell group and showed that levels of preproenkephalin mRNA are also decreased, whereas no significant changes in cholecystokinin, beta-preprotachykinin, and angiotensinogen mRNA levels could be detected. Thus, corticosterone decreases some neuropeptide mRNA levels and has no influence on others in this cell group. Tyrosine hydroxylase mRNA hybridization is also unaffected in this part of the nucleus. In a second group of experiments, the cell-type specificity of corticosterone influences was examined. It was found that while the hormone depresses CRH mRNA levels in parvicellular neurons, it increases such levels in PVH neurons with descending projections, in certain magnocellular neurosecretory neurons, and in a part of the central nucleus of the amygdala, whereas no influence was detected in the rostral lateral hypothalamic area. Furthermore, the stimulatory effects of corticosterone have different threshold levels in different cell groups. Thus, in different types of neurons, corticosterone may increase, decrease, or have no influence on CRH mRNA levels. In contrast, while corticosterone depresses vasopressin mRNA levels in parvicellular CRH neurons, it has no obvious effects on vasopressin mRNA levels in magnocellular or descending neurons; as with CRH, the effects of corticosterone on vasopressin mRNA levels are cell-type specific. In a third series of experiments it was shown that glucocorticoid receptor and mineralocorticoid receptor mRNAs are found in all three cell types in the PVH and that corticosterone tends to produce modest increases in mRNA levels for both receptors. Finally, it was shown that unilateral catecholamine-depleting knife cuts do not change mRNA levels for any of the neuropeptides (or steroid hormone receptors) examined here, although dramatic changes in neuropeptide levels themselves have been shown.4+
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PMID:Differential steroid hormone and neural influences on peptide mRNA levels in CRH cells of the paraventricular nucleus: a hybridization histochemical study in the rat. 256 87

Many parvocellular neurons in the paraventricular nucleus of the hypothalamus express high levels of corticotropin releasing factor (CRF) or vasopressin following adrenalectomy. To determine whether glucocorticoids feed back directly on these neurons, a mouse monoclonal antibody directed against the rat liver glucocorticoid receptor was used in combination with polyclonal antisera directed against either vasopressin or CRF to permit simultaneous visualization of either peptide with glucocorticoid receptor-like immunoreactivity (IR). Rats were adrenalectomized (ADX) for 2 weeks to optimize numbers of vasopressin - and CRF-IR neurons. Six hours prior to sacrifice, a separate group of adrenalectomized rats was treated with corticosterone (40 mg/kg). This short-term replacement resulted in nuclear localization of glucocorticoid receptor-like-IR but did not attenuate the increased numbers of CRF- and vasopressin-IR neurons observed after adrenalectomy. It was therefore possible to visualize vasopressin- or CFR-IR and nuclear glucocorticoid receptor-like-IR simultaneously. Cell counts of double-labeled neurons in the paraventricular nucleus of the hypothalamus (PVH) demonstrated that glucocorticoid receptor-like-IR is colocalized in virtually all the CRF and vasopressin immunoreactive parvocellular neurons studied, which respond to adrenalectomy by increased peptide expression. These data suggest that a major feedback effect of glucocorticoids on the hypothalamic-pituitary-adrenal axis is exerted directly within nuclei of CRF and vasopressin neurons.
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PMID:Demonstration of glucocorticoid receptor-like immunoreactivity in glucocorticoid-sensitive vasopressin and corticotropin-releasing factor neurons in the hypothalamic paraventricular nucleus. 326 Feb 89

Quantitative in vitro autoradiography, cytosol receptor assay in punched brain tissue, and immunocytochemistry have revealed that the glucocorticoid receptor is present in the rat supraoptic nucleus (SON). Based on its binding characteristics the receptor appears to be the type II glucocorticoid receptor. With the use of a monoclonal antibody against purified liver glucocorticoid receptor, immunostaining was found in magnocellular neurosecretory neurons in the SON, but not in magnocellular neurons in the paraventricular nucleus. Immunoreactive cells seem to be concentrated in ventral parts of the SON where vasopressin cells were previously shown to be located. One to 2 weeks after bilateral adrenalectomy, there was a substantial decrease in glucocorticoid receptor immunostaining in magnocellular as well as other types of neurons in various brain regions. Administration of synthetic glucocorticoids (RU 28362 or dexamethasone) induced a robust increase in the intensity of immunostaining in cell nuclei of neurosecretory cells. The presence of glucocorticoid receptors in the SON suggests that glucocorticoids may affect vasopressin synthesis or/and secretion through a direct action on magnocellular neurons.
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PMID:Glucocorticoid receptor in magnocellular neurosecretory cells. 333 8

The hippocampus is the principal target site in the brain for adrenocortical steroids, as it has the highest concentration of receptor sites for glucocorticoids. The aged rat has a specific deficit in hippocampal glucocorticoid receptors, owing in large part to a loss of corticoid-sensitive neurons. This deficit may be the cause for the failure of aged rats to terminate corticosterone secretion at the end of stress, because extensive lesion and electrical stimulation studies have shown that the hippocampus exerts an inhibitory influence over adrenocortical activity and participates in glucocorticoid feedback. We have studied whether it is the loss of hippocampal neurons or of hippocampal glucocorticoid receptors in the aged rat that contributes most to this syndrome of corticosterone hypersecretion. To do this, we used two model systems for producing reversible glucocorticoid receptor depletion in the hippocampus, and we found that depletion of receptors without inducing cell loss results in corticosterone hypersecretion. Furthermore, correction of the receptor deficit results in normalization of corticosterone secretion. These results focus attention on the hippocampus as an important glucocorticoid sensor in relation to the stress response. They also provide important new physiological correlates for the remarkable plasticity of the hippocampal glucocorticoid receptor system, which is under independent control by corticosterone and by vasopressin.
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PMID:Glucocorticoid-sensitive hippocampal neurons are involved in terminating the adrenocortical stress response. 659 9

The aged rat shows a decline in hippocampal corticosterone receptors and dysfunction in learning and adrenocortical physiology previously linked to glucocorticoid effects upon the hippocampus. The Brattleboro rat, congenitally lacking vasopressin, also has a low number of hippocampal glucocorticoid receptors, as well as learning and endocrine impairments similar to those seen in the aged. Centrally acting vasopressin analogues correct the receptor loss in the hippocampus in the Brattleboro rat but do not influence the hippocampal receptor deficit in the aged rat. Quantitative and high resolution autoradiographic procedures were utilized to characterize the glucocorticoid receptor deficit in the aged and Brattleboro rats. Quantitative autoradiography showed that in both aged and Brattleboro subjects, losses in receptors were most extreme in the pyramidal layer of the CA3a region. High resolution autoradiography revealed striking differences in the cellular basis of the receptor losses. Brattleboro rats had decreased binding of [3H]corticosterone per neuron, whereas aged subjects, in addition, had significant losses in the number of corticosterone-concentrating neurons. Taken together, our findings indicate that the glucocorticoid receptor deficit in the Brattleboro rat probably represents a vasopressin-influenced defect in the synthesis or degradation of the receptor, whereas in the aged rat the deficit originates from loss of both receptor per neuron and the steroid-concentrating neurons themselves, and thus is most likely a permanent and pharmacologically insensitive deficit.
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PMID:Do vasopressin-related peptides induce hippocampal corticosterone receptors? Implications for aging. 672 43

The binding of [3H]corticosterone to receptors in cytosol of several brain regions and of [3H]dexamethasone to receptors in pituitary cytosol was measured after chronic treatment of homozygous diabetes insipidus rats (Ho-Di) with various neuropeptides. All rats were adrenalectomized 24 h before sacrifice for depletion of endogenous adrenal hormones and at that time administration of the peptides was discontinued. At sacrifice the rats were perfused with saline to remove plasma transcortin from the tissues. The apparent maximal binding capacity for corticosterone and dexamethasone was significantly lower in hippocampus and anterior pituitary (36.8% and 39.2%, respectively) of Ho-Di rats than of homozygous nondiabetic rats (Ho-No) of the same strain. In contrast, the neurointermediate pituitary lobe of Ho-Di rats had more than twice as many (211%) binding sites, whereas neither receptor capacity in hypothalamus and septum nor plasma transcortin in these rats were significantly different from those in Ho-No rats. Treatment of Ho-Di rats with arginine-vasopressin, des-glycinamide arginine vasopressin, or 1-desamino-8-D-arginine-vasopressin daily for 1 week resulted in an elevation of receptor capacity in hippocampus and anterior pituitary near the level observed in nondiabetic controls. No effects on the other brain regions, the neurointermediate pituitary lobe, and on plasma transcortin were observed with these peptide treatments. Administration of oxytocin and ACTH-(4-10) did not affect receptor binding. It is concluded that in the Ho-Di Brattleboro rat the glucocorticoid receptor system in the hippocampus and in the anterior pituitary is selectively affected by neuropeptides related to vasopressin.
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PMID:Vasopressin-related peptides increase the hippocampal corticosterone receptor capacity of diabetes insipidus (Brattleboro) rats. 705 79

1. Several years ago, investigators described the effects of infantile handling on the development of hypothalamic-pituitary-adrenal (HPA) responses to stress in the rat. Rat pups exposed to brief periods of innocuous handling early in life showed reduced HPA responses to a wide variety of stressors, and the effect persists throughout the life of the animal. These effects are robust and provide an excellent model for understanding how early environmental stimuli, which are external to the organism, alter neural differentiation and, thus, neuroendocrine responsivity to stress. 2. This paper reviews the endocrine mechanisms affected by early handling and our current understanding of the neural transduction of environmental events and their effects at the level of the target neurons (in the hippocampus and frontal cortex). 3. In brief, handling serves to increase glucocorticoid receptor gene transcription, increasing sensitivity to glucocorticoid negative feedback regulation and, thus, altering the activity within hypothalamic corticotropin-releasing factor/vasopressin neurons. Together these changes serve to determine neuroendocrine responsivity to stress.
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PMID:Molecular basis for the development of individual differences in the hypothalamic-pituitary-adrenal stress response. 825 6

Glucocorticoids inhibit and glucocorticoid deficiency increases vasopressin (AVP) release in vivo. To determine whether the effect of glucocorticoids is hypothalamic and mediated via a glucocorticoid receptor, explants of the hypothalamic-neurohypophysial system were used to measure AVP release during agonist and antagonist exposure. Explants from adult rats, which contained AVP neurons of the supraoptic nucleus with axonal projections terminating in the neural lobe but excluded the paraventricular nucleus, were perifused with an osmotic stimulus (increase of 5 mosmol/h over 6 h) in the absence or presence of corticosterone (100 micrograms/dl) or with corticosterone (100 micrograms/dl) in the absence or presence of the glucocorticoid antagonist RU-486 (10 microM). AVP release was not increased during osmotic stimulation in the presence of corticosterone (Cort) and was 20-30% lower than osmotically stimulated release observed in the absence of Cort. RU-486 reversed the inhibitory effect of corticosterone on AVP release. No changes in AVP mRNA content were detected. These results suggest that Cort inhibits osmotically stimulated AVP release by a direct effect within the hypothalamus and/or neurohypophysis. This effect is mediated by the glucocorticoid receptor through either genomic or nongenomic mechanisms.
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PMID:Corticosterone inhibition of osmotically stimulated vasopressin from hypothalamic-neurohypophysial explants. 903 4

Glucocorticoids are known to exert multiple effects upon neuronal systems and neuronal gene expression but the molecular mechanisms through which these effects are mediated are largely undefined. In this study, a transgenic mouse model that expresses a bovine vasopressin transgene was used to investigate the mechanisms by which this neuropeptide gene is repressed by glucocorticoids. Using both northern analysis and a reverse transcriptase polymerase chain reaction assay, depletion of glucocorticoids with the 11,beta-hydroxylase inhibitor metyrapone was shown to result in a dexamethasone-reversed increase in ectopic adrenal transgene messenger RNA levels. This result shows that sequences within the confines of the 3.5 kb transgene are sufficient to mediate repression by glucocorticoids, and indicates the involvement of a type II glucocorticoid receptor mechanism which is independent of cellular context. Evidence for the involvement of cis-acting repressive elements in the proximal 5' flanking sequence was obtained in further studies in which bovine transgene constructs were shown to be negatively regulated by dexamethasone in 293 cells. The further demonstration that recombinant glucocorticoid receptor binds to a vasopressin promoter fragment in an in vitro electrophoretic mobility shift assay provided additional evidence of a direct mechanism of repression. Both in vitro studies were consistent with the presence of a glucocorticoid regulatory element within the region -300 to 155 of the transcription start site. The use of an in vivo transgenic system combined with in vitro analyses of gene promoter fragments enabled the characterization of the molecular mechanisms which effect physiological changes in vasopressin gene expression, and provided evidence of a direct mechanism of repression mediated by sequences within the vasopressin gene promoter.
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PMID:Repression of vasopressin gene expression by glucocorticoids in transgenic mice: evidence of a direct mechanism mediated by proximal 5' flanking sequence. 917 83


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