Disease relevance of CORTICOSTERONE

• Mutations in CYP11B2 result in aldosterone synthase (corticosterone methyloxidase) deficiency, an isolated defect in aldosterone biosynthesis that can cause hyponatremia, hyperkalemia, and hypovolemic shock in infancy and failure to thrive in childhood [1].
• These mice had increased adipose levels of corticosterone and developed visceral obesity that was exaggerated by a high-fat diet [2].
• Infection of hypophysectomized mice with Newcastle disease virus caused a time-dependent increase in corticosterone and interferon production [3].
• On the other hand, the 163-171 fragment did not cause any of several inflammation-associated metabolic changes inducible by the whole IL-1 beta molecule in vivo: hypoferremia, hypoglycemia, hyperinsulinemia, increase in circulating corticosterone, SAA and fibrinogen, decrease in hepatic drug-metabolizing enzymes [4].
• The subcutaneous administration of 0.075 or 0.75 nmol oCRF/h to intact rats for 7 d also resulted in elevations of both plasma ACTH and corticosterone levels comparable to those measured after a 24-h exposure to the releasing factor, as well as dose-related hypertrophy of the adrenals and increases in pituitary ACTH content [5].

Psychiatry related information on CORTICOSTERONE

• Insulin and corticosterone, which are known to affect hypothalamic NPY and CRH expression, were not different between these two groups, making it unlikely that they can account for the differences in either feeding behavior or hypothalamic peptide expression [6].
• Here, we show that sleep deprivation inhibits adult neurogenesis at a time when circulating levels of corticosterone are elevated [7].
• Prenatally-stressed (PS) rats also show behaviour consistent with depression, including a phase-shift in their circadian rhythm for corticosterone, sleep abnormalities, a hedonic deficit and greater acquisition of learned helplessness under appropriate conditions [8].
• Rats that exhibit high rates of locomotor activity and sustained exploration in such an environment also exhibit high concentrations of stress-induced plasma corticosterone, linking this behavior to the stress system [9].
• After 24 hr of maternal deprivation, significant elevations in ACTH and the naturally occurring glucocorticoid corticosterone (CORT) are observed during the stress-hyporesponsive period [10].

High impact information on CORTICOSTERONE

• Crhr2 also appears to modify the recovery phase of the HPA response, as corticosterone levels remain elevated 90 minutes after stress in Crhr2-/- mice [11].
• In contrast to the PC2 null phenotype, these mice show markedly elevated circulating ACTH and corticosterone levels, with adrenocortical expansion [12].
• Here we show that in mice lacking Crhr1, the medulla of the adrenal gland is atrophied and stress-induced release of adrenocorticotropic hormone (ACTH) and corticosterone is reduced [13].
• Despite normal survival in utero, all Ftz-F1 null animals died by postnatal day 8; these animals lacked adrenal glands and gonads and were severely deficient in corticosterone, supporting adrenocortical insufficiency as the probable cause of death [14].
• Formation of well-vascularized tissue at the site of transplantation was associated with stable levels of cortisol in the blood, replacing the mouse glucocorticoid (corticosterone) [15].

Chemical compound and disease context of CORTICOSTERONE

• Anti-MIF antibody prevented P-mediated up-regulation of TNF-alpha, improved TNBS colitis, and enhanced plasma corticosterone [16].
• In all paradigms, a rise in fat intake, from 10 to 30%, is associated with reduced levels of insulin and corticosterone and normal glucose levels, whereas a further increase in fat ingestion (>30%) leads to hyperglycemia along with greater adiposity [17].
• In one family, a severely affected member had hypertension and hypokalemic alkalosis associated with increased plasma concentrations of corticosterone and deoxycorticosterone [18].
• It is postulated that lack of the cyclic nucleotide-dependent kinase activity of the protein kinase enzyme may be responsible for the loss of cyclic AMP-regulated corticosterone synthesis in adrenocortical carcinoma cell [19].
• Finally, the general nature of the CORT potentiation of damage was supported by the markedly different postulated mechanisms of toxicity of KA and 3-AP [20].

Biological context of CORTICOSTERONE

• Hypothalamic neuropeptide Y stimulates food intake, decreases thermogenesis, and increases plasma insulin and corticosterone levels making it a potential target [21].
• Although maternally separated rats show normal basal levels of corticosterone, the suppression of cell proliferation in these rats can be reversed by lowering corticosterone below the control value [22].
• Therefore, it is likely that factors in addition to leptin are involved in the regulation of the circadian rhythm of corticosterone [23].
• Circadian rhythms of leptin, corticosterone, and thyroxine were regulated by food intake in adult mice [23].
• CRH and POMC gene expression and blood levels of ACTH, CORT, and PRL were normalized within 1-3 d of removal of suckling pups [24].

Anatomical context of CORTICOSTERONE

• Recombinant IRAP specifically inhibited IL-1 bioactivity on T cells and endothelial cells in vitro and was a potent inhibitor of IL-1 induced corticosterone production in vivo [25].
• Hormones could also contribute to the control of this transmitter choice, and McLennan et al. recently reported that corticosterone treatment of whole superior cervical ganglia (SCG) greatly inhibited the cholinergic development of these ganglia in culture [26].
• 1. Corticosterone binds with high affinity to MRs predominantly localized in limbic brain (hippocampus) and with a 10-fold lower affinity to GRs that are widely distributed in brain [27].
• Lymphocytes appear to be the most likely source of an adrenocorticotropin-like substance that is responsible for the increased corticosterone, since spleen cells from the virus-infected, but not from control or dexamethasone-treated, hypophysectomized mice showed positive immunofluorescence with antibody to adrenocorticotropin-(1-13 amide) [3].
• The rat adrenal hormone corticosterone can cross the blood-brain barrier and bind to two intracellular receptor populations in the brain--the mineralocorticoid and glucocorticoid receptors [28].

Associations of CORTICOSTERONE with other chemical compounds

• The calcium-dependent slow afterhyperpolarization is reduced in hippocampal slices from adrenalectomized rats, and it is increased after in vivo or in vitro administration of the adrenal steroid, corticosterone [29].
• Today it is generally accepted that parvocellular neurones of the hypothalamic paraventricular nucleus control the secretion of corticotropin and corticosterone by synthesising and releasing both the corticotropin-releasing hormone and vasopressin (AVP) [30].
• Inhibition of thymic corticosterone production or blockade of the glucocorticoid receptor with RU-486 resulted in enhanced TCR-mediated, antigen-specific deletion of immature thymocytes [31].
• This was achieved by continuous delivery of aldosterone (1 microgram X 100 g-1 X d-1) from an osmotic minipump or of corticosterone (2 pellets of 20 mg each), implanted subcutaneously either at adrenalectomy or 7 d later, when Na-K-ATPase activity reached its nadir [32].
• The obese mice with low levels of hypothalamic ObR also show elevated plasma levels of leptin, glucose, insulin, and corticosterone [33].

Gene context of CORTICOSTERONE

• Here, we report a 1.95 A crystal structure of the MR ligand binding domain containing a single C808S mutation bound to corticosterone and the fourth LXXLL motif of steroid receptor coactivator-1 (SRC1-4) [34].
• Inhibition of ACTH secretion by ion channel blockers or corticosterone has potent inhibitory effects on percentages of CRH-bound cells [35].
• We also show that corticosterone is normally induced in IL-6-deficient mice, demonstrating that IL-6 is not required for the activation of the hypothalamic-pituitary-adrenal axis [36].
• In addition, IL-1ra and 35F5 significantly blocked the ability of IL-1 to stimulate egress of PMN from bone marrow, to induce a transient neutrophilia, and to elevate serum levels of hepatic acute phase proteins, IL-6, and corticosterone [37].
• It does this by maintaining ACTH and corticosterone levels, not only under stress but also under basal conditions [38].

Analytical, diagnostic and therapeutic context of CORTICOSTERONE

• A similar effect is seen after adrenalectomy, indicating a U-shaped dose-response dependency of these cellular responses after the exposure to corticosterone [27].
• Corticosterone: a critical factor in an opioid form of stress-induced analgesia [39].
• However, the subsequent refractory phase that is characteristic of rats that have recovered from EAE induced by active immunization with MBP is not associated with chronically elevated corticosterone levels [40].
• The intravenous infusion of 0.75 nmol oCRF/h to intact rats over a 24-h period was accompanied by a peak of ACTH and corticosterone secretion that occurred during the first 90 min of administration of the releasing factor, followed by a decrease to lower, but still above control, values [5].
• METHODS: Messenger RNA from 11 beta-OHSD1 and 11 beta-OHSD2 was assessed by reverse-transcription polymerase chain reaction; activity was assessed by measuring the interconversion of corticosterone to dehydrocorticosterone [41].

References