Biomedical subjects
Publications and source records attributed to T A Obut.
In male rats exposed to repeated stress, the decrease in stress reactivity produced by subcutaneous injection of dehydroepiandrosterone sulfate (recorded by the decrease in stress-induced concentrations of corticosterone and adrenocorticotropic hormone in blood plasma) was observed 1-6 days postinjection and involved central regulatory mechanisms.
13-14-day old mice of ICR and CBA strains were given a single intraperitoneal injection of nitrosoethylurea (80 mg/kg) or diethylnitrosamine (50 mg/kg). 2 weeks later, they were given drinking water containing phenobarbital (1 g/L) or thyroxine (2 mg/L). The control mice were given only tap water. 29.4% of male and 42.1% of female ICR mice who had received nitrosoethylurea died of leukemia within 3-6 months after the carcinogen treatment. There was no case of leukemia in mice treated with diethylnitrosamine. Nitrosoethylurea induced 3-more often lung adenomas than diethylnitrosamine. Phenobarbital and thyroxine did not affect development of either leukemias or lung adenomas. By contrast, phenobarbital significantly elevated the number and size of hepatic lesions, whereas thyroxine markedly decreased them in all the experiments. The total and free thyroxine levels were significantly decreased in the blood of mice given phenobarbital and increased in mice given thyroxine. The data obtained indicate that thyroid hormones suppress tumor development in the mouse liver and that the promotion of hepatic tumoro-genesis by phenobarbital is presumably caused by the elimination of this suppressing effect of the thyroid hormones.
Acute stress was accompanied by reduction of 11-dehydrocorticosterone to corticosterone in male rats. The reverse reaction predominated during repeated stress and increased after administration of dehydroepiandrosterone sulfate. Treatment with mu-opioid receptor antagonist naltrexone in a dose of 0.1 mg/kg 20 min before administration of dehydroepiandrosterone sulfate abolished this effect.
Dehydroepiandrosterone sulfate prevented the increase in corticosterone level in rats induced by repeated exposure to stress. The mu-opioid receptor blocker naltrexone administered in a dose of 0.1 mg/kg 20 min before treatment with dehydroepiandrosterone sulfate abolished the effect of this agent. Dehydroepiandrosterone sulfate and naltrexone had no effect on rats after acute stress.
Effects of dehydroepiandrosterone sulfate (DHEAS, 30 mg/kg, i/p, 4 and 28 hours after injection) on CBA/Lac male mice with increased level of anxiety resulting from chronic (20-days) social confrontations in two behavioral anxiety-estimated tests, were studied. The anxiolytic effect of DHEAS was discovered within 4 hours after injection in the "partition test" of social interactions and within 28 hours in "plus-maze test". Naltrexone (0.25 mg/kg, for 20 min before DHEAS injection) blocked this effect.
The dehydroepiandrosterone sulfate (DHEAS) effect on stress-reactivity and the role of mu-opioid receptors in it, were studied. The experiments were carried out in male rats. The shuttling in single or in multiple (19 days, for 1 hour a day) regimes served as the experimental stress influences. The estimation of stress-reactivity was carried out by the plasma corticosterone level. It had been shown that the subcutaneous injection of dehydroepiandrosterone sulfate in rats reduced the stress-induced increase in corticosterone levels under the multiple influences, whereas naltrexone (0.1 mg/kg, for 20 min before DHEAS injection) blocked this effect. There were no effects of DHEAS or naltrexone on corticosterone levels under the single stress influences.
The review deals with the biological significance of the reticular area of the adrenal cortex, which is to be clarified. The author's own findings and the data available in the literature indicate that the androgens dehydroepiandrosterone and dehydroepiandrosterone sulfate that are secreted in the reticular area play an important role in ensuring the body's full stable adaptation to stress and simultaneously preventing stress-associated abnormalities, such as atherosclerosis, diabetes, immunodefficiency, hypertension, allergies, and cancer. The study of the physiological mechanisms of action of dehydroepiandrosterone and dehydroepiandrosterone sulfate is promising for academic and practical medicine and basic biology.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
A single stress effect activated the fascicular zone whereas repeated stress effects activated both the fascicular and the reticular zones in male rats. Therefore, these zones seem to have different modes of regulation despite the fact that their common basic regulating agent is ACTH. A new scheme of regulation of the reticular zone in repeated stress effects, has been presented.
Explore the source record for details and available documents.
In adult male mice CBA and C57BL there were revealed differences in the morphometric characteristics of the subcellular organization of hepatocytes, as well as in the indices of functional capacity of the adrenal cortex and the rate of metabolism of steroid hormones in the liver. In animals of the strains under study the levels of steroid hormones production by the adrenal cortex and the rate of gross metabolism of steroid hormones in the liver were characterized by inverse relationship. Structural-functional indices of the adrenal cortex and the liver are supposed to cause different liver responses in these strains of mice to the influence of the alterating factors.
Explore the source record for details and available documents.
Effects of dehydroepiandrosterone sulfate (DHEAS, 30 mg/kg, i.p., 4 and 28 hours after the injection) were studied in CBA/Lac male mice different in the level of anxiety resulting from repeated social victories (winners) or social defeats (losers) in 10 daily agonistic confrontations. The losers demonstrated high level of anxiety estimated by the "partition" test. The DHEAS and saline injections had different effects on winners, losers, and intact mice. DHEAS prevented the development of anxiety in losers 28 hours after the injection. In these experimental conditions DHEAS exerted no effect on winners. It was concluded that the DHEAS effect depends on the psychoemotional state of an animal. The anxiolytic effect of the exogenous DHEAS may be also characteristic of the endogenous hormone secreted by the adrenal glands and in the central nervous system.
Effects of dehydroepiandrosterone sulfate (DHEAS, 30 mg/kg, i.p., 4 and 28 hours after an injection) on CBA/Lac male mice with increased level of anxiety resulting from chronic (20-day) social confrontations were studied in two behavioral tests. The anxiolytic effect of DHEAS was observed both 4 and 28 hours after an injection in the partition test of social interactions and in the plus-maze test.
The effects of dehydroepiandrosterone sulfate (DHEAS) on the extinction of passive avoidance was studied on C57Bl/6J mice with aggressive and submissive behavioral stereotypes. Administered in a single dose 30 mg/kg one day or one hour before training, DHEAS selectively blocked the extinction of the conditioned habit in submissive mice, thus favoring its retrieval. The probable mechanism of this phenomenon can be related to a decrease in the level of inhibiting control in the GABAergic system.
It was shown that injections of NMDA receptor antagonist dizocilpine and neurosteroid dehydroepiandrosterone sulfate (DHEAS) and sequential injections of these substances had different effects on learning and extinction of passive avoidance in aggressive and submissive mice. In aggressive mice, dizocilpine impaired and DHEAS did not change learning and retention. However, being injected after dizocilpine, DHEAS blocked the defect of memory trace retrieval induced by dizocilpine. In submissive mice, dizocilpine impaired learning and prolonged extinction of the learned habit. Injection of DHEAS prolonged the extinction in a similar way. Under conditions of sequential injections, DHEAS did not change the suppressive effect of dizocilpine on learning and was not effective in prolongation of extinction.
Explore the source record for details and available documents.