Effect of dexamethasone on Fc γ receptor expression in foetal and neonatal rat gut

Summary When injected into 12-day-old suckling rats, dexamethasone caused a precocious disappearance of Fc receptors from enterocytes of the proximal small intestine. However, dexamethasone appeared to be necessary for the maintenance or production of such receptors in foetal rat gut cultured in vitro.Supported by an award from the Science and Engineering Research Council.     

Number of glucocorticoid receptors in lymphocytes and their sensitivity to hormone action

The study demonstrated a decreased level of glucocorticoid receptors (GR) in peripheral blood lymphocytes from hypercholesterolemic subjects, and an elevated level in patients with acute myocardial infarction. In the lymphocytes with a high GR number, dexamethasone inhibited [3H]-thymidine and [3H]-acetate incorporation into DNA and cholesterol, respectively, in the same manner as in the control cells. On the other hand, a decreased GR number resulted in a less efficient dexamethasone inhibition of the incorporation of labeled compounds. These data showed that the sensitivity of lymphocytes to glucocorticoids changed only with a decrease of GR level.     

Steroid hormones and the cardiovascular system: Direct actions of estradiol,progesterone, testosterone,gluco- and mineralcorticoids,and soltriol [vitamin D] on central nervous regulatory and peripheral tissues

Summary Knowledge of steroid hormone sites of action and related effects in cardiovascular and neural regulatory tissues is reviewed. Evidence for nuclear receptor sites is derived mainly from autoradiographic studies with relatively intact tissues and some biochemical studies with tissue homogenates.In the heart and in the walls of blood vessels, estradiol, dihydrotestosterone, corticosterone, aldosterone, dexamethasone, and soltriol (vitamin D) show nuclear binding. In the brain and spinal cord, neuronal regions associated with cardiovascular regulation contain nuclear receptors in specific patterns for each steroid hormones, including progesterone and soltriol. These data indicate that all steroid hormones exert direct actions on the cardiovascular system at its different levels of organization, thus enabling adjustment to the changing demands during reproduction (gonadal steroids), stress (adrenal steroids), and solar seasons (vitamin D-soltriol).     

Steroid hormones and the cardiovascular system: direct actions of estradiol, progesterone, testosterone, gluco- and mineralcorticoids, and soltriol [vitamin D] on central nervous regulatory and peripheral tissues

Knowledge of steroid hormone sites of action and related effects in cardiovascular and neural regulatory tissues is reviewed. Evidence for nuclear receptor sites is derived mainly from autoradiographic studies with relatively intact tissues and some biochemical studies with tissue homogenates. In the heart and in the walls of blood vessels, estradiol, dihydrotestosterone, corticosterone, aldosterone, dexamethasone, and soltriol (vitamin D) show nuclear binding. In the brain and spinal cord, neuronal regions associated with cardiovascular regulation contain nuclear receptors in specific patterns for each steroid hormones, including progesterone and soltriol. These data indicate that all steroid hormones exert direct actions on the cardiovascular system at its different levels of organization, thus enabling adjustment to the changing demands during reproduction (gonadal steroids), stress (adrenal steroids), and solar seasons (vitamin D-soltriol).     

Effect of cortexolone on the feedback action of dexamethasone.

Cortexolone in a dose of 1 mg/100 g body wt., administered to rats prior to dexamethasone, prevented dexamethasone from suppressing stress-induced ACTH-release without interfering with the effect of dexamethasone on the resting plasma corticosterone level.     

Dexamethasone enhances CTLA-4 expression during T cell activation

T cell activation is enhanced by the costimulatory interaction of B7 on antigen-presenting cells and CD28 on T cells, resulting in long-term T cell proliferation, differentiation and production of large amounts of cytokines, such as interleukin (IL)-2. CTLA-4 is a co-stimulation receptor that shares 31% homology with CD28 and binds B7 family members with higher affinity. CTLA-4 is transiently expressed intracellularly and on the cell surface following activation of T cells. We have studied the kinetics of CTLA-4 expression and the effects of dexamethasone on CTLA-4 expression during T cell activation in cultures of mouse spleen cells stimulated by a mixture of immobilized anti-CD3 and anti-CD28 monoclonal antibodies (anti-CD3/CD28 mAb) or concanavalin A (ConA). CTLA-4 expression peaked on day 2 and returned to background levels after 7 days. Dexamethasone was found to potentiate CTLA-4 expression in a dose-dependent manner with an EC₅₀ effective concentration 50%) of about 10⁻⁸ M. In contrast, other immunosuppressive agents, such as rapamycin or cyclosporin A had no or an inhibitory effect on CTLA-4 expression, respectively. Dexamethasone also stimulated CD28 expression, but inhibited IL-2R expression during anti-CD3/CD28 mAb-induced mouse splenic T cell activation. Western blot analyses of lysates of activated mouse T cells showed that dexamethasone increased CTLA-4 protein levels twofold during anti-CD3/CD28 mAb-induced activation. Dexamethasone also enhanced CTLA-4 messenger RNA twofold as quantified by ribonuclease protection assay. The effects of dexamethasone on CTLA-4 expression were glucocorticoid-specific and completely inhibited by the glucocorticoid receptor antagonist mifepristone (RU486), indicating that the effect of dexamethasone on CTLA-4 expression is mediated through the glucocorticoid receptor. In conclusion, the immunosuppressive agent dexamethasone actually stimulates CTLA-4 expression, which is involved in downregulation of T cell activation. Received 19 May 1999; received after revision 13 July 1999; accepted 13 July 1999     

In vitro effect of dexamethasone in conversion of 4-14C progesterone in the fetal rat adrenal glands

Summary It was found that dexamethasone in vitro inhibited the synthesis of corticosterone and aldosterone.This research was supported by Grant No. IV/3 from the Scientific Fund of the Socialist Republic of Croatia, Zagreb Yugoslavia.     

Dexamethasone-induced neutrophilia. Negative correlation with increased plasma adrenaline concentrations

Summary Maximal increments in adrenaline and dexamethasone (DXM) plasma concentrations were observed c15 (T₅₀ 40 min) and 30 (T₅₀ 210–240 min) minutes after an i.v. DXM dose (6 mg/m² BSA) in man. There appears, however, to be no direct interaction between these agents in the development of induced neutrophilia, which occurs c240 min postinjection.Acknowledgments. The authors wish to thank Mrs C. Ditzler, Merck Sharp & Dohme Research Laboratories, USA, for determining the plasma dexamethasone concentrations J. M. M. is currently on sabbatical leave from McGaw Laboratories, USA. C. R. B. is a Rhodes scholar.     

Corticosteroid effects on cholinergic enzymes in ethanol-treated fetal brain cell cultures

In the presence of ethanol, corticosterone and dexamethasone inhibit choline acetyltransferase and acetyl-cholinesterase activities in cultured fetal brain cells of the rat. These results suggest that corticosteroids may have an important influence on the activity of cholinergic enzymes in the fetal brain may antagonize the effects of ethanol in this setting.     

Corticosteroid effects on cholinergic enzymes in ethanol-treated fetal brain cell cultures

Summary In the presence of ethanol, corticosterone and dexamethasone inhibit choline acetyltransferase and acetylcholinesterase activities in cultured fetal brain cells of the rat. These results suggest that corticosteroids may have an important influence on the activity of cholinergic enzymes in the fetal brain and may antagonize the effects of ethanol in this setting.     

Effect of glucocorticoids on the appearance of gamma-glutamyl transpeptidase activity in primary cultures of adult rat hepatocytes

Primary cultures of adult rat liver parenchymal cells showed a progressive rise of gamma-glutamyl transpeptidase (GGT) activity (E.C. 2.3.2.2) after the first 5 days of culture. The presence of dexamethasone and other synthetic glucocorticoids in the culture medium partially prevented this increase.     

Electronmicroscopic identification of type C particles in cultured murine neuroblastoma.

Monolayer of murine neuroblastoma were treated with dexamethasone and examined by electronmicroscopy. Most of the treated cells were morphologically differentiated and exhibited type C virus particles which were budding from the cell surface. This in vitro system may be of great value for exploring the oncogenic potential of the virus, and its possible role in cell differentiation.     

Natural killer-like activity in human cultured lymphoid cells propagated in the presence of interleukin-2: acquired resistance to prostaglandin E2- or dexamethasone-mediated suppression

The cytotoxic activity of human peripheral blood lymphocytes against the natural killer-sensitive target K562 was suppressed both by prostaglandin E2 and dexamethasone. On the other hand, cultured lymphoid cells propagated in the presence of interleukin-2 showed strong cytotoxic reactivity against K562 targets, and were resistant to prostaglandin E2- or dexamethasone-mediated suppression.     

Attempt at activating mouse intracisternal type A particles by iododeoxyuridine and dexamethasone]

In this study we have compared the effects of Iododeoxyridine (IUdR) and dexamethasone on different Mouse cell lines to determine any differences in their actions on intracisternal A-type particles (IAP). Among the nine cell lines studied only four responded to IUdR stimulation by a subsequent augmentation of IAP. No similar activating effect was detected with dexamethasome treatment.     

Systemic candidiasis from Candida albicans colonizing the gastrointestinal tract of mice.

Reproducible induction of systemic Candida infection was achieved by treating mice in which Candida colonization had been established in the gastrointestional tract by aminobenzylpenicillin treatment. Systemic candidiasis was induced in these mice by X-ray irradiation followed by immunosuppressive doses of dexamethasone or X-ray irradiation followed by immunosuppressive doses of trypan blue. Macrophages seem to play an important role in thie systemic infection.     

Induction, by 5-bromo-2'-deoxyuridine, of a "foamy" virus previously undetected in hamster cells transformed by SV40]

TSV5 clone 2 cells in normal conditions of culture contain only an expressed RNA virus (R-type virus). However, exposure of the cells to 5-bromo-2'-deoxyuridine with dexamethasone, induced synthesis of a syncitium-forming ("Foamy") virus. In other hamster cell lines, the same treatment fails to induce a "foamy" virus. The origin of this "foamy" virus is discussed.     

Effects of testosterone propionate on LH and testosterone concentrations before and after the injection of gonadoliberin in young bulls pre-treated with dexamethasone]

This preliminary study has been performed on four young twin bulls, one pair aged 6 months and the other one aged 12 months. Plasma LH and testosterone were assayed from frequent blood sampling. Testosterone propionate (TP) following dexamethasone treatment did not significantly influence the LH response to gonadoliberin compared to the twin controls, although testosterone concentrations were high in those TP treated animals.     

Dexamethasone-induced neutrophilia. Negative correlation with increased plasma adrenaline concentrations

Maximal increments in adrenaline and dexamethasone (DXM) plasma concentrations were observed c15 (T50 40 min) and 30 (T50 210-240 min) minutes after an i.v. DXM dose (6 mg/m2 BSA) in man. There appears, however, to be no direct interaction between these agents in the development of induced neutrophilia, which occurs c240 min postinjection.     

Changes in the blood cortisol levels during the first week of life in calves (Bos taurus) and lambs (Ovis aries)]

At birth, the plasmatic level of cortisol is very variable and very high in the new-born Calf or the newborn Lamb. This level diminishes within one day and then varies between 10 and 30 ng/ml during the six following days. In the Calf, the secretion of cortisol can be directly stimulated by ACTH or inhibited at the level of the hypothalamic and hypophyseal system with dexamethasone on the day following birth.     

Systemic candidiasis fromCandida albicans colonizing the gastrointestinal tract of mice

Summary Reproducible induction of systemicCandida infection was achieved by treating mice in whichCandida colonization had been established in the gastrointestinal tract by aminobenzylpenicillin treatment. Systemic candidiasis was induced in these mice by X-ray irradiation followed by immunosuppressive doses of dexamethasone or X-ray irradiation followed by immunosuppressive doses of trypan blue. Macrophages seem to play an important role in this systemic infection.