Glucocorticoids stimulate cholesteryl ester formation in human smooth muscle cells.

The aim of the present study was to investigate the effect of synthetic glucocorticoid dexamethasone (Dex) on cholesterol esterification in cultured human smooth muscle cells (SMC). In labeled SMC, Dex stimulated the esterification of [3H]cholesterol in a dose-dependent manner. This effect was specific for glucocorticoid hormones and could be inhibited by cycloheximide (3 ng/mL), actinomycin D (10(-5) mol/L), and the specific glucocorticoid antagonist RU 486 (10(-8) mol/L). When plasma membrane was selectively labeled with trace quantities of [3H]cholesterol (0.25 microCi/mL, 1 hour, 10 degrees C), Dex (10(-8) mol/L) caused a net flux of free [3H]cholesterol into the cells. Moreover, Dex (10(-8) mol/L, 24 hours) stimulated the esterification of sterols, newly synthesized from [14C]mevalonate (10 microCi/mL, 4 hours) and lowered the amount of [14C]sterols susceptible for cholesterol oxidase. The incorporation of [14C]oleic acid into cholesteryl esters was markedly higher in Dex-pretreated SMC than in the control cells (2.1 +/- 0.07 and 1.4 +/- 0.1 pmol/h/microgram protein, respectively, P < .01). At the time, cholesteryl ester hydrolysis in Dex-treated cells was reduced (72 +/- 8 pmol cholesteryl esters/h per milligram versus 130 +/- 10 in the control cells). HDL3-mediated [3H]cholesterol efflux was also inhibited in Dex-treated cells; moreover, HDL3 (40 micrograms/mL, 24 hours) had practically no effect on [3H]cholesteryl ester content in Dex-treated SMC but caused a 50% reduction of [3H]cholesteryl esters in the control cells. Thus, in human SMC glucocorticoids alter the redistribution of cholesterol between the pools of free and esterified cholesterol, paralleled by the change in acyl coenzyme A: cholesteryl acyltransferase and neutral cholesteryl ester hydrolase activities, leading to the impaired HDL3-mediated cholesterol efflux.

Comparative study of the activity and composition of HDL3 in Russian and American men.

Previous studies conducted within the framework of the Lipid Research Clinics Program showed a strong inverse correlation between high-density lipoprotein cholesterol (HDL-C) level and coronary heart disease (CHD) risk in American male populations, whereas in Russian populations such a correlation was less pronounced. It was assumed that HDL was less protective of CHD in Russian than in American males. This study compared the functional activity and lipid composition of HDL3 isolated from the blood plasma of men with low, normal, and high HDL-C levels from Moscow (Russia) and Seattle (United States) populations. Results obtained showed that American HDL3, irrespective of the plasma HDL-C level, had higher activity in stimulating both [3H]cholesterol and cholesterol mass efflux from cholesterol-loaded fibroblasts and in suppressing cellular cholesterol esterification when compared with Russian HDL3. American HDL3 remained more active than Russian HDL3, even when apolipoprotein E-containing particles were removed from HDL3 by heparin-Sepharose affinity chromatography. Russian and American 125I-HDL3 had similar binding to high-affinity cell-surface sites, but Russian HDL3 had a higher nonspecific binding component compared with American HDL3. This study demonstrates for the first time potential functional differences between HDL particles isolated from Russian and American populations. The lower activity of Russian HDL3 in promoting cellular cholesterol efflux may partly explain the higher CHD risk in the Russian population compared with the American one.

[Insulin and C-peptide secretion after physical exertion in men with newly manifested stenocardia and chronic ischemic heart disease]. / Sekretsiia insulina i C-peptida pri fizicheskoi nagruzke u muzhchin s vpervye voznikshei stenokardiei i khronicheskoi ishemicheskoi bolezn'iu serdtsa.

Variation in insulin and C peptide levels was examined in patients with angina of new onset and chronic coronary heart disease. Insulin secretion was increased in all coronary patients, as compared to the controls, and hormonal response to additional stress was abnormal in postmyocardial infarction patients. It is demonstrated that insulin secretion is already changed at early stages of coronary disease, and the pattern of change is presented.

[Relation of the levels of thyroid hormones and cortisol and the degree of systolic arterial pressure in 11- and 12-year-old boys]. / Sviaz' kontsentratsii tireoidnykh gormonov i kortizola s urovnem sistolicheskogo arterial'nogo davleniia u mal'chikov 11-12 let.

An epidemiologic evaluation of relationships between arterial BP changes, and thyroid and adrenocortical hormones was carried out in eleven- and twelve-year-old boys. Different patterns of correlation were demonstrated between plasma thyrotropic hormone, thyroid hormones and cortisol levels, on one hand, and systolic BP variation, on the other. There was a correlation between thyroid hormones and cortisol in these groups. The results suggest that even slight changes in thyroid and adrenal function may promote disorders of BP regulation.

[Heterogeneity of cardiac glucocorticoid receptors]. / Geterogennost' gliukokortikoidnykh retseptorov serdtsa.

The work presents the main results obtained in the investigation of properties and distribution of the glucocorticoid cardiac receptors as well as mutual conversions of different forms of the glucocorticoid-receptor complexes. The receptors have been found in hearts of various kinds of animals. The glucocorticoid receptor activity is distributed approximately evenly in the myocardium of the left and right ventricles and auricles. The receptors have been found both in isolated myocytes and in endothelium cells. Methods of chromatography can successfully be used in decomposition of the glucocorticoid-receptor complex to heterogenic components. The role of some factors in the mechanism of the functioning of the receptor system is discussed.

[Calcium and the permissive effect of glucocorticoids: the role of glucocorticoids in an adrenaline-induced increase in the rate of calcium absorption by the ventricular tissue of the rat heart]. / Kal'tsii i permissivnyi éffekt gliukokortikoidov: o roli gliukokortikoidov v indutsiruemom adrenalinom uvelichenii skorosti pogloshcheniia kal'tsiia tkan'iu zheludochkov serdtsa krys.

It was demonstrated in rat experiments that the ability of the myocardial ventricles to increase 45Ca absorption after the injection of adrenaline was disturbed on the 3rd--5th day following adrenalectomy. The decrease in sensitivity to adrenaline occurred in two phases and was delayed essentially after a fall in the concentration of glucocorticoids in circulation. Chronic in vivo injection of hydrocortisone (2.5 mg per rat) into these animals for 3--5 days restored the effect of catecholamine to a great extent. The restorative effect was weaker when the rats were given a single intravenous hydrocortisone infusion 6 hours before being killed. Increase of the single intravenous dose of the hormone to 5 and 7.5 mg per rat reduced its effect. The authors assume that the described permissive effect of glucocorticoids is determined not by their direct interaction with the cytoplasmic membrane but by hormone induced intracellular synthesis of proteins capable of participating in the regulation of permeability to ions.

Corticosteroidal regulation of the glucocorticoid-binding capacity of rat heart cytoplasmic fraction.

The effects were studied of variations in blood corticosteroid levels on the glucocorticoid-binding capacities of two types of complex-forming substances, whose presence in the myocardium had been established in previous studies. The hormone binding was assessed by the method of adsorption of free forms of steroids on activated dextrancoated charcoal with application of Scatchard's analysis. The binding capacity was tested both in the presence of endogenous steroids and in cytoplasmic fraction made free of the hormones. After adrenalectomy, experimental stress, and administration of exogenous glucocorticoids the concentration of the complex-forming substance I changed in parallel with changing blood transcortin levels. This finding corroborates the concept that the complex-forming substance I is an intercellular (and possibly partially also intracellular) pool of transcortin or a transcortin-like protein; this pool regulates the accessibility of glucocorticoids to the cytoreceptor proper. The intracellular concentration of the complex-forming substance II (performing the function of receptor) changed only little with varying corticosteroid levels, and variations in its binding capacity evidently resulted from shifts in the equilibrium between the "occupied" and "free" findings sites as well as in the distribution of this protein between the cytoplasmic and nuclear fractions.

[Binding of glucocorticoids by a transcortin-like protein in the cytoplasmic fraction of rat myocardium]. / Sviazyvanie gliukokortikoidov transkortinopodobnym belkom tsitoplazmaticheskoi fraktsii miokarda krys.

Myocardial cytosol of adult adrenalectomized rats bound specifically 3H-corticosterone and 3H-hydrocortisone and did not bind the synthetic 9alpha-fluoroglucocorticoid (dexamethasone) in vitro at 0-4 degrees. The specific binding of dexamethasone was not also found in the cytosol of neonatal rats. Heating of myocardial cytosol of adrenalectomized rats within 10 min at 60 degrees led to the complete loss of the glucocorticoid-binding activity. Treatment of the cytosol within the same period but at the temperature lower than 55 degrees did not affect its binding capacity. 3H-corticosterone-cytoreceptor complex was precipitated by ammonium sulphate at 40-60% of saturation. The complex was eluted from a column of Sephadex G-150 by solutions with both low (0.015 M KCl) and high (0.4 M KCl) ionic strength as the alone peak. This fraction corresponded by molecular weight to the transcortin complex. The data obtained and the results of our previous investigations suggest that myocardial glucocorticoid-binding cytoplasmic protein is related to transcortin-like cytoreceptors.