[The role of the mediator and hormonal links of the sympathetic-adrenal system in the anxiolytic effect of close to physiological doses of L-thyroxine under stress]. / Znachenie mediatornogo i gormonal'nogo zven'ev simpatiko-adrenalovoi sistemy v realizatsii anksioliticheskogo effekta blizkikh k fiziologicheskim doz L-tiroksina pri stresse.

OBJECTIVE: To study an effect of small doses of L-thyroxine on the level of anxiety in animals under stress and to analyze the role of the mediator and hormonal links of the sympathetic-adrenal system in its implementation. MATERIAL AND METHODS: The study was performed on 78 white outbread male rats. Stress was modeled using the «time deficit¼ method. Chemical sympathectomy was performed by intraperitoneal injection of guanetidine at a dose of 30 mg/kg for 28 days. Bilateral adrenalectomy was performed according to the method of Y.M. Kabak. L-thyroxine was injected intragastrically for 28 days in small doses (1.5-3 µg/kg). The level of anxiety was determined in the «open field¼ test. The content of iodine-containing thyroid hormones (ICTH) in the blood serum was evaluated by the enzyme immunoassay. RESULTS: It has been found that stress activates thyroid function (an increase in the concentration of ICTH by 23-44%, p<0.01) and increases the level of anxiety in animals (an increase in the total resting time by 21%, p<0.05 and the resting time in periphery - by 25%, p<0.01). Chemical sympathectomy does not affect the growth of anxiety in rats who have undergone stress, whereas adrenalectomy contributes to its increase (an increase in the total resting time and the resting time in periphery by 15 and 14%, p<0.05). The injection of L-thyroxine minimizes the increase in the content of ICTH in the blood (by 16-27%, p<0.05) and has an anxiolytic effect under stress (prevents an increase in the total resting time and the resting time in periphery). Both chemical sympathectomy and, especially, adrenalectomy somewhat minimize, but do not completely prevent the implementation of the anti-anxiety effect of L-thyroxine under stress. CONCLUSION: In the formation of the anti-anxiety effect of ICTH, their central stress-limiting influence is important, limiting the mobilization of both the mediator and hormonal links of the sympathetic-adrenal system. The role of the latter in the implementation of the stress-protective effect of thyroid cancer is not decisive.

[Effect of the thyroid status on the proteinases/inhibitors system under stress].

Тhe alarm-stage of stress reaction (аn hour after the stress of swimming of rats in a cage during an hour) is characterized by the stimulation of trypsinе-like activity (TLA) in the liver, and especially in the blood. At the resistance stage (48 hours after the stress) there is normalization of TLA in the blood and limitation of its growth in the liver. At the stage of exhaustion (an hour of stress during 10 days) the most significant increase of TLA in the liver and blood develops. Experimental hypothyroidism (25 mg/kg merkazolil within 20 days) per se causes a reduction of TLA, defines more pronounced stimulation of proteolysis in the alarm-stage, prevents its normalization at the resistance-stage, and promotes its excessive activation at the stage of exhaustion. Introduction of small doses of L-thyroxine (1.5-3.0 g/kg during 28 days) does not affect the system of proteolysis, limitis the increase of TLA at the alarm- and exhaustion stages, prevents its stimulation at the resistance-stage. The dependence of the changes in the proteases/inhibitors system under stress from the level of iodine-containing thyroid hormones in the blood is due to their influence on the activity of endogenous proteinase inhibitors (a1-antitrypsin and a2-macroglobulin) and on the permeability of lysosomes membranes.

[Effect of iodine-containing thyroid hormones on the histostructure of rat liver under the stress].

Experiments with 130 outbred male rats weighing 220-250 g have show that stress "free swimming in a cage" (FSC) affects the histological structure of the liver as early as in 1 h. FSC occurred in standard plastic cages (5 animals) filled with water to a height of 15 cm and topped with a grid. One hour after FSC (the alarm-stage) caused dystrophy of hepatocytes and increased blood flow to the liver lobules, which also continued at the resistance-stage (48 h after the FSC). At the exhaustion-stage (daily 1-hour stress for 10 days) there were even greater hepatocytes dystrophy, necrosis, and their microcirculatory disturbances in the lobules. The introduction of merkazolil (intragastrically 25 mg/kg for 20 days) per se altered the histostructure of the liver tissue and under stress aggravates the microcirculatory changes, dystrophy and necrosis of the hepatocytes. Small doses of L-thyroxine (intragastrically 1.5-3.0 µg/kg for 28 days) minimized the histological signes of the liver damage at all stages of the stress response. Consequently, the iodine-containing thyroid hormones limit the disturbance of the microstructure of the liver caused by stress.

[Effect of thyroid status on the system proteolysis under stress].

Introduction of merkazolil to in rats (25 mg/kg 20 days), causing reduction of iodine containing thyroid hormones levels (ITH) in the blood, reduces the trypsin-like activity (TLA) and the activity of α1-antitrypsin (α1-AT) and α2-macroglobulin (α2-MG) in the liver and blood; in the alarm-stage of stress reaction (1 hour after swimming in a cage) it defines more pronounced than that in euthyroid animals stimulation of proteolysis due to the decline of α1-AT and α2-MG activity, in stage of resistance (48 hours) it prevents the normalization of TLA, α1-AT and α2-MG activity, which took place in the stress at the euthyrosis; in the stage of exhaustion (1 hour of the stress within 10 days) promotes to the most significant activation of the proteolysis owing to profound inhibition of the α1-AT and α2-MG. The introduction of L-thyroxine (1.5-3.0 µg/kg 28 days) does not change the concentration of ITH in the blood and it does not affect the proteolyis system; in the alarm- and exhaustion stages it limits the increase of the TLA, in the stage of re-istance prevents it, eliminating the depression of aα1AT and aα-MG activity. The results demon-trate a new aspect of the participation of ITH in the body anti-stress system --heir effect on pro-ease/inhibitor system.

[Iodine-containing thyroid hormones increases the motor activity of rats under stress].

It is established that alarm-stage of stress reaction (1 hour after the swimming of rats in a cage within 1 hour) is characterized by a decrease of total vertical motor activity (MA) and by the chan- ge of behavior structure--disappearance of racks without support on the board of "open field" and a central horizontal part of MA as well as an increase in physical endurance of rats; stage of resistan- ce (48 hours after the stress)--the restoration of motor reactions of animals, and stage of exhaustion (1 hour within 10 days of stress)--its oppression. Introduction of merkazolil (25 mg/kg, 20 da- ys) causes a fall of level of iodine-containing thyroid hormones (ITH) in the blood and causes a significant reduction of all types of MA and change of the structure of behavior in the alarm-stage, practically eliminating its normalization in stage of resistance and provokes its greatest violation in a stage of exhaustion of stress reaction. Introduction of L-thyroxine (1.5-3.0 µg/kg 28 days) does not change the ITH concentration in the blood, increases MA of rats, and provides its higher level and maintaining of the structure of behavior in all stages of stress reaction.