Disease relevance of CORTICOSTERONE

• After 4 d of infusion, dietary intake and weight gain were significantly higher in the Cort and AL groups than in the TNF and TNF+Cort groups [1].
• We report here that corticosterone (CT) protects cardiomyocytes from apoptotic cell death induced by doxorubicin (Dox), an antineoplastic drug known to induce cardiomyopathy possibly through reactive oxygen species production [2].
• These data provide support for a specific mode of action for i.c.v. alpha-MSH(1-13), namely blockade of APRs with no impact on acute hyperthermia or increased levels of CORT produced during IS [3].

High impact information on CORTICOSTERONE

• The lymphocytes incubated with CORT may have an increased sensitivity to IL-2 because 1) CORT suppressed IL-2 production throughout the culture period, and 2) an anti-IL-2R mAb completely blocked both control and CORT-treated anti-TCR-induced lymphocyte proliferation [4].
• Surprisingly, we found that the principal glucocorticoid of the rat, corticosterone (CORT), potently enhanced anti-TCR-induced lymphocyte proliferation after 2 to 3 days in culture, followed by inhibited cell growth after 5 to 7 days [4].
• Analyses of 20,000 gene expression sequences using Affymetrix high-density oligonucleotide array found that CT caused up-regulation of 140 genes and down-regulation of 108 genes over 1.5-fold [2].
• The cytoprotection induced by CT is within the range of physiologically relevant doses [2].
• Orally fed rats were divided into 3 treatment groups: continuous infusion of TNF-alpha (TNF; 100 microg x kg(-1) x d(-1)), corticosterone (Cort; 50 microg x g(-1) x d(-1)), or both (TNF+Cort) [1].

Biological context of CORTICOSTERONE

• Our data suggest that CT induces a cytoprotective effect on cardiomyocytes in association with reprogramming gene expression and induction of bcl-xL gene [2].
• As well, bicuculline prevented the inhibition of sexual behavior induced by CS injection [5].
• Intravenous injections of ANG II antagonist had no significant effects on mean AP or heart rate in control or Cort-treated rats [6].
• Changes in plasma corticosterone (CS) and mean arterial blood pressure (MABP) were also detected [7].
• Consistent with a previous experiment, implants of CORT and ALDO in the hypothalamic paraventricular nucleus (PVN) were effective in stimulating food intake [8].

Anatomical context of CORTICOSTERONE

• The central finding was that the CORT-evoked acceleration of the proliferative response in vitro was attenuated in splenic T cells from animals that had received the high-dose CORT treatment in vivo [9].
• In the presence of I, A, and C, EGF increased the level of alpha-casein mRNA in pregnant mouse mammary gland explants, but not in rats. kappa-Casein mRNA sequences in mouse mammary gland explants were also significantly increased by EGF in the presence of I, A, and C, but in rat mammary gland explants, the increase was less [10].
• However, whereas CORT and P4 influenced the ADX-induced increase in the transcription of both types of corticosteroid receptors in the hippocampus, these were unaffected by THP [11].
• Optic nerve cytosol fractions displayed substantial high-affinity binding of both dexamethasone (DEX) and corticosterone (CORT) that, like GPDH, was elevated approximately two fold in degenerating nerves [12].
• AS significantly increased UI, adrenal gland weight (AGW), GL, CK activity, and CORT, whereas G. biloba significantly reduced them [13].

Associations of CORTICOSTERONE with other chemical compounds

• Explants from mammary glands of virgin rats and pregnant rats and mice were cultured under serum-free conditions in the presence of various combinations of the hormones insulin (I), aldosterone (A), corticosterone (C), PRL, and epidermal growth factor (EGF) [10].
• ICV injections of TRH caused dose-dependent increases in plasma CS, but did not further increase HPA responses when injected together with 5-HT [14].
• The inhibitory effects of confinement stress or corticosterone (CS) injections on newt sexual behaviors were blocked by pretreatment of newts with mercaptopropionic acid, a blocker of GABA synthesis [5].
• Replacement with subcutaneous CORT implants (100-mg pellets) for 7 days following ADX rats did not affect CR number, but caused a 38% decrease in GR number compared to control animals (cholesterol-treated, 7-day-ADX rats) [15].
• The synergy of CORT with T(3) on tadpole tail resorption may depend on the accelerated accumulation of GR transcripts in this tissue during metamorphosis, which may be driven by rising plasma thyroid hormone titers [16].

Gene context of CORTICOSTERONE

• The ADX + CORT group showed significantly greater increases in both CRH and AVP mRNA levels in the PVN compared to sham rats [17].
• In repeated stress, the sham groups showed robust increases in PVN CRH and AVP mRNA levels despite high levels of plasma CORT [17].
• In contrast, in the presence of I, A, C, and PRL, EGF inhibited the induction of both alpha- and kappa-casein mRNA sequences in tissue from rats and mice [10].
• These data indicate that a CORT-mediated decrease in hippocampal and hypothalamic glucocorticoid receptor mRNA levels is not the only mechanism contributing to the maintenance of a robust HPA response after repeated stress [17].
• IL-6 bioactivity in serum was not significantly changed by CS treatment, but increased 50 times upon injection of rhIL-1 beta. rhIL-1 beta caused a significantly lower induction of serum IL-6 levels in CS pretreated rats (9-fold) [18].

Analytical, diagnostic and therapeutic context of CORTICOSTERONE

• Western blot analyses revealed that CT induced an elevation of bcl-xL but not bcl-2 or proapoptotic factors bax, bak, and bad [2].
• However, the mortality rate was high (> or = 70%) in these experiments and plasma CS elevation persisted in HxCB-treated adrenalectomy survivors [19].
• Castration failed to reduce the elevation of plasma CS in HxCB-treated male mice [19].
• Microinjection of ANG II intracerebroventricularly produced a significantly larger increase in AP in Cort-treated rats than in control rats [6].
• Sixteen female rats were divided into four equal groups (control and 3 experimental groups implanted with tricalcium phosphate lysine drug delivery systems (TCPL) charged with either 50mg selenomethionine (Se), 50 mg corticosterone (C), or 50 mg of both C and Se) [20].

References