CHANGES IN THE CONCENTRATION OF PROLACTIN IN THE BLOOD CAUSED BY SULFUR DIOXIDE ON THE ARCUATE NUCLEUS OF THE HYPOTHALAMAUS

ABSTRACT

The article studies the effects of toxic stress created by sulfur dioxide and mechanical stress created by electrode insertion on the arcuate nucleus of the hypothalamus on the activity of prolactin (PRL) in the blood. The strength of EEG waves in the arcuate nucleus of the hypothalamus changes in a biphasic manner due to toxic stress. In the post-model period, EEG waves do not normalize. The toxic stress dramatically increases the concentration of PRL in the blood, and this level does not normalize in the post model period. Since the inhibitory effect of the hypothalamic dopaminergic system on PRL-synthesizing cells in the adenohypophysis is eliminated, the synthesis and secretion of PRL into the blood increases. As a result of the mechanism stress caused by the insertion of an electrode, the activity of PRL in the blood is higher than normal. Thus, studying the relationship between the hypothalamic-pituitary systems in extreme conditions provides an opportunity to solve various practical and theoretical problems.

АННОТАЦИЯ

В статье изучено влияние экспериментального токсического стресса на фоне диоксида серы и механического стресса - путем введения электрода в дугообразное ядро гипоталамуса на активность пролактина (ПРЛ) в крови. Мощность волн ЭЭГ в дугообразном ядре гипоталамуса изменяется двухфазно вследствие токсического стресса. Токсический стресс резко увеличивает концентрацию пролактина в крови, этот уровень не нормализуется в пост модельном периоде. Устранение ингибирующего влияния гипоталамической дофаминергической системы на синтезирующие ПРЛ клетки аденогипофиза, увеличивает синтез и секрецию ПРЛ в кровь. Активность ПРЛ в крови также становится выше нормы из-за механического стрессового воздействия путем введения электрода в дугообразное ядро гипоталамуса. Таким образом, изучение взаимосвязи гипоталамо-гипофизарной системы в экстремальных условиях дает возможность решению различных практических и теоретических задач.

Keywords: Hypothalamus, hormone, sulfur dioxide, toxic stress.

Ключевые слова: Гипоталамус, гормон, диоксид серы, токсический стресс.

INTRODUCTION

From the point of view of modern directions of neurophysiology and neuroendoc rinology, the study of the role of the integrative activity of the hypothalamus is an actual problem. However, in the modern globalized world, the interaction between the monoaminergic functional activity of the organism and the neuroendocrine system, as well as the neurophysiologic mechanisms underlying this relationship, have not been sufficiently studied. On the other hand, there are many extreme factors that have a negative impact on most functions of the organism [1, p.374-375; 2, p.79-80; 3, p.77-78; 4, p.753-754; 5, p.102, p.104 ; 6, p.38]. In extreme situations, the realization of stress reactions occurs with the participation of the arcuate nucleus, one of the integrative centers of the hypothalamus. Since this center regulates homeostatic processes and adaptive reactions, it is important to study the neurohormonal connection in extreme situations. When harmful substances from the environment enter the body in inadequate quantities, they cause the development of serious functional disorders, as well as have a significant negative impact on human health [7, p.1-2 ;8, p.149 ]. It is also relevant to conduct research on the functional regulation mechanism of the hypothalamus and changes in the hormonal activity of the endocrine system against the negative effects of these factors [9, p.869; 10, p.155]. The negative effect of most harmful substances on the body occurs either as a result of direct damage to the endocrine glands or as a result of indirect disruption of the functions of the endocrine system [11, p.294-295;12, p.3142]. Therefore, proper assessment of such factors plays an important role in predicting, detecting, and preventing negative factors affecting human health.

Purpose of the study is to study the role of changes in the activity of the arcuate nucleus of the hypothalamus in the regulation of prolactin in extreme situations of various origins.

MATERIAL AND METHODS

The experiments were conducted on 35 female rabbits weighing 2.5±0.5 kg. The animals were adapted to the experiment for 3-4 days before the main experiment. Before starting the experiment, an electrode was inserted into the arcuate nucleus of the hypothalamus, the studies were conducted on the 7 groups shown below. The 1-st group of rabbits were in an intact (normal) state; the 2-nd group of rabbits were exposed to sulfur dioxide at a dose of 120 PPM for 30 minutes every day for 5 days; the 3-rd group of rabbits were exposed to sulfur dioxide for 15 days; the 4-th group of rabbits were exposed to sulfur dioxide every day for 30 days. The rabbits of 5-th, 6-th and 7-th groups were exposed to the toxic stress model for 5, 15 and 30 days, respectively, then they were released for 5, 15 and 30 days and were not exposed to any effects. The mechanical effect of electrode insertion in each group was also studied. The frequency and amplitude of electroencephalographic (EEG) waves of the arcuate nucleus of the hypothalamus of rabbits were recorded during the toxic stress model and in the post-model period by the “Neuro-spectrum2” (Russia) EEG device. The concentration of PRL in the blood was determined by the immunoenzyme method. The determination of markers was carried out using a fully automated Bio Screen MS-2000 analyzer (USA). The quantitative data obtained from the experiments were processed in accordance with modern instructions [13, p.1-250]. Statistical analysis was performed using Microsoft Excel, and the significance of differences between means was assessed using the paired Student's t-test.

RESULTS AND DISCUSSION

As a result of our studies, it was determined that the changes in the arcuate nucleus of the hypothalamus caused by the experimental toxic stress caused by sulfur dioxide change the amplitude and frequency rhythms of the hypothalamus EEG waves of different nature and in two-phases. The changes in these indicators are more profound during the application of toxic stress for a month. Compared to the beginning of the experiment, very sharp differences are obtained between the amplitude and frequency rhythms of the waves. In the post-model period of toxic stress application no normalization of the EEG wave indicators is observed. These changes are better directed than in the normal state, depending on the duration of the toxic stress effect. The toxicity we applied has both an activating and a depressant effect on the amplitude and frequency rhythms of EEG waves. Since the mechanism of interaction between the arcuate nucleus of the hypothalamus and other systems is disrupted by the effect of toxic stress, the activity of the adenohypophysis PRL hormone in the blood also changes sharply. Thus, while the absolute value of PRL in the blood is 13.2±0.4 ng/ml in the normal state, on the 5th day of the stress model, the absolute value of this quantity increased to 29.0±1.1 pg/ml, and the relative value was 119.7%, (p<0.001) (Table 1). Slightly different results occur due to the mechanical effect of the electrode insertion into the arcuate nucleus. Thus, due to the mechanical effect of the electrode insertion into the arcuate nucleus, the absolute value of PRL increased to 20.6±0.7 ng/ml, which is 56.1% (p<0.001) higher than the norm (Table 1).

Thus, while in normal conditions the mean value of PRL in the blood was 13.2±0.4 ng/ml, on the 5th day of the stress model the absolute value of this quantity increased to 29.0±1.1 pg/ml, and the relative value was 119.7% (p<0.001) (Table 1). Due to the mechanical effect of the electrode insertion into the arcuate nucleus, the mean value of PRL was 20.6±0.7 ng/ml, which was 56.1% (p<0.001) higher than the norm. After creating the stress model for 5 days, the mean value of PRL in the group released for 5 days was 24.9±0.4 ng/ml, and the relative value was 88.6% (p<0.001) (Table 1). In this group, the mean and relative values ​​of PRL in the blood after the mechanical effect of the electrode insertion into the arcuate nucleus practically did not change from the level in the previous group (Table 1).

 Table 1.

The effect of toxic stress, post-stress period and mechanical effect of electrode insertion into the arcuate nucleus of the hypothalamus on blood prolactin concentration, created by 5 days of sulfur dioxide exposure (n=5)

Note: Reliability with norm- p<0.001

On the 15th day of the experiment, the absolute value of PRL in the blood increased further due to the stress effect, reaching 33.2±1.5 pg/ml, and the relative increase was 151.5% (p<0.001) (Table 2). The mean value of PRL due to the mechanical effect of the electrode insertion into the arcuate nucleus was 19.3±1.1 ng/ml, which was 46.2% (p<0.001) higher than the norm (Table 2).

Table 2.

The effect of toxic stress, post-stress period, and mechanical effect of electrode insertion into the arcuate nucleus of the hypothalamus on blood prolactin concentration, created by 15 days of sulfur dioxide exposure(n=5)

Note: Reliability with norm- p<0.001

After the 15-day stress model was created, the absolute value of PRL in the group released for 15 days was 24.7±0.6 ng/ml, and the relative value was 87.1%, (p<0.001) (Table 2). After the mechanical effect of the electrode insertion into the arcuate nucleus, the absolute value of PRL in the blood was 19.7±0.5 ng/ml, and the relative value was 49.3%, (p<0.001) (Table 2).

Table 3.

Effects of toxic stress induced by 30 days of sulfur dioxide exposure, post-stress period, and mechanical effect of electrode insertion into the arcuate nucleus of the hypothalamus on blood prolactin concentration(n=5)

Note: Reliability with norm- p<0.001

The increase in the absolute value of PRL in the blood due to the effect of toxic stress continued on the 30th day of toxic stress and became even more pronounced. Thus, under the influence of the stress model, its absolute value amounted to 40.4±1.6 pg/ml, and its relative value was 206.1% (Table 3).

Thus, the results obtained show that due to such changes occurring in the nervous system during the period of sulfur dioxide exposure, the amount of PRL in the blood compared to the norm is 119.7% <0.05 on the 5th day of the experiment; 151.5%, p<0.05 on the 15th day; and 206.61%, p<0.05 on the 30th day.

Also, the increase in PRL blood levels due to toxic stress was 88.6%, p<0.05; 87.1%, p<0.05; 131.1%, p<0.05, respectively, in animals released during the post-model period. As can be seen, the PRL blood levels do not fully normalize. These results prove that after the PRL regulatory system of the hypothalamus is exposed to toxic and mechanical effects, the inhibition process of PRL synthesizing cells in the adenohypophysis is eliminated and PRL secretion into the blood increases.   

Thus, toxic stress, changing the activity of the arcuate nucleus of the hypothalamus, disrupts the synthesis of hormones and their secretion into the blood in any link of this system. In extreme conditions, the study of the interaction of the hypothalamic-pituitary system and their pathogenetic mechanisms and the discovery of the role of regulatory mechanisms can allow solving various practical problems. Therefore, the study of the interaction of the hypothalamic-pituitary system and their pathogenetic mechanisms, as well as the discovery of the role of these regulatory mechanisms in extreme conditions can allow solving various practical problems. The strength of the rhythms of EEG waves in the arcuate nucleus of the hypothalamus changes in different directions due to the toxic and mechanical effects of sulfur dioxide.But toxicity causes more profound changes. Toxicity has both an activating and a depressant effect on the power of EEG waves. Changes in the arcuate nucleus of the hypothalamus change the activity of hormones. The amount of PRL is 119.7% - 151.5% - 206.6% higher than normal. In the post-model period, it is 88.6% higher; 87.1% - 131.1%5) higher.

DISCUSSION

It has been established that the amplitude and frequency of EEG waves in the arcuate nucleus of the hypothalamus changes biphasically after exposure to experimental toxic stress. No normalization of EEG waves is observed in the post-model period. These changes are partially directed towards the normal state depending on the duration of the toxic stress effect. Such changes in the arcuate nucleus of the hypothalamus in animals released during the toxic stress effect and during the post-model period increase the concentration of PRL in the blood. As can be seen, the amount of PRL in the blood does not completely normalize. These results prove that since the inhibitory effect of the hypothalamic dopaminergic system on PRL-synthesizing cells in the adenohypophysis is eliminated [6.p.38;14,p.94 ], the synthesis of PRL in the adenohypophysis and its secretion into the blood increase. Therefore, the activity of prolactin (PRL) in the blood changes due to the effects of toxic stress created by sulfur dioxide, as well as mechanical stress created by the insertion of an electrode, on the arcuate nucleus of the hypothalamus.However, slightly different results are obtained from the effect of mechanical stress. Even after the mechanical stress of inserting an electrode into the arcuate nucleus, the amount of PRL in the blood is still higher than normal.

Thus, the arcuate nucleus of the hypothalamus has a complex structure that plays a key role in the regulation of the biological functions of the body, and plays an essential role in the endocrine regulation of the pituitary-gonadal system. Sulfur dioxide, acting on the arcuate nuclei of the hypothalamus, changes the secretion of hormones in any link of this system. Therefore, the study of the interaction of the hypothalamic-pituitary system and their pathogenetic mechanisms, as well as the discovery of the role of these regulatory mechanisms in extreme conditions, can allow solving various theoretical and practical problems.

 Conclusions:

1.Due to the toxic stress effect caused by sulfur dioxide, the amplitude and frequency rhythm strength of EEG waves in the arcuate nucleus of the hypothalamus change in a biphasic manner. No normalization of EEG waves is observed in the post-model period.

2.Such changes occurring in the arcuate nucleus of the hypothalamus in animals released during the toxic stress effect and the post-model period increase the concentration of PRL in the blood. The amount of PRL in the blood does not fully normalize.

3. Due to the toxic stress effect, the inhibitory effect of the hypothalamic dopaminergic system on PRL-synthesizing cells in the adenohypophysis is eliminated, and the synthesis of PRL in the adenohypophysis and its secretion into the blood increase.

4.PRL activity in the blood changes due to the effect of mechanical stress created by the introduction of the electrode on the arcuate nucleus of the hypothalamus.

5.The obtained results allow us to reveal the role of the regulatory mechanism of the interaction of the hypothalamic-pituitary system in extreme situations.

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