CHANGES IN THE ACTIVITY OF ADENOHYPOPHYSEAL-GONODAL SYSTEM HORMONES IN THE BLOOD DUE TO TOXIC STRESS INDUSED BY SULFUR GAS ON THEARCQUATE NUCLEUS OF THE HYPOTHALAMUS

ABSTRAСT

The article studies the changes in the activity of the hormones of the adenohypophyseal-gonadal system due to the effect of sulfur dioxide on the arcuate nucleus of the hypothalamus. It was found that in toxic stress conditions and in the post-stress period, the amplitude and frequency of the EEG waves in the arcuate nucleus of the hypothalamus changes in different directions compared to the norm. Toxicity has both an activating and a depressing effect on the waves compared to the norm. Since this effect disrupts the regulatory mechanism of the hormones of the adenohypophyseal-gonadal system, the activity of follicle-stimulating hormone (FSH), prolactin (PRL) and estradiol (E2) in the blood changes. In the post-model period, the activity of hormones does not normalize. The arcuate nucleus of the hypothalamus, in addition to being a complex structure involved in the regulation of biological functions of the organism, plays an essential role in the endocrine regulation of the adenohypophyseal-gonadal system.

Therefore, conducting research in the direction of studying the interaction of the hypothalamic-pituitary-gonadal system in extreme situations of various origins and revealing the role of their regulatory mechanisms may allow solving various theoretical and practical problems.

АННОТАЦИЯ

В статье исследуются изменения активности гормонов аденогипофизарно-гонадальной системы, вызванные воздействием диоксида серы на дугообразное ядро гипоталамуса. Установлено, что в условиях токсического стресса и в постстрессовый период амплитуда и частота ЭЭГ-волн в дугообразном ядре гипоталамуса демонстрируют двунаправленные изменения относительно нормальных уровней, оказывая как возбуждающее, так и тормозящее действие. Поскольку это действие нарушает регуляторный механизм гормонов аденогипофизарно-гонадальной системы, изменяется активность фолликулостимулирую щего гормона (ФСГ), пролактина (ПРЛ) и эстрадиола (Е2) в крови. В постмодельный период активность гормонов не нормализуется. Дугообразное ядро ​​гипоталамуса, помимо того, что является сложной структурой, участвующей в регуляции биологических функций организма, играет существенную роль в эндокринной регуляции аденогипофизарно-гонадальной системы. Таким образом, исследование взаимодействие гипоталамо-гипофизарно-гонадальной системы в экстремальных ситуациях различного происхождения и выявление роли их регуляторных механизмов может позволить решить различные теоретические и практические проблемы.

Keywords: hypothalamus, arcuate nucleus, EEG waves, hormone, sulfur dioxide, toxic stress.

Ключевые слова: гипоталамус, дугообразное ядро, волны ЭЭГ, гормон, диоксид серы, токсический стресс.

INTRODUCTION

In the modern world, the role of the functional activity of the central nervous system in the regulation of the endocrine system in various physiological and pathological conditions of the body is widely studied. However, in the modern globalized world, the interaction between the monoaminergic and peptidergic functional activity of the body and the neuroendocrine interaction and the neurophysiological and neuroendocrinological mechanisms of this relationship have not been sufficiently studied  [2,s.1-2; 8,s.869]. Also, harmful environmental agents cause the development of serious morphofunctional pathologies in the organism and have a negative impact on human health  [1,s. 8119;3,s.70;4,s.37; 5,s.94;6,s.55; 7,s.102]. The negative impact of most harmful factors on the body is due to various disruptions in the functions of the endocrine system [8,s.869; 10,s.1;11,s.3142; 12,s.294]. It is important to conduct research into the mechanism of functional regulation of the hypothalamus against the negative effects of these factors [4,s,37;5,s,948,s.869].  Correct assessment of such factors can play an important role in predicting and preventing the negative impact on human health[14,s.9;15,s.1-2].  On the other hand, it is known that the realization of stress reactions of various etiologies occurs by the integrative centers of the hypothalamus. The arcuate nucleus, which is the neuroendocrine center of the hypothalamus, regulates vital homeostatic processes, the realization of stress reactions and adaptive reactions in normal conditions  [4,s,37;8,s.869]. In the arcuate nucleus of the hypothalamus, neurotransmitters and neuropeptides of various nature are synthesized. Also, hypophysiotropic neurons that synthesize the central hormone of stress are located here. For this reason, we considered it necessary to conduct research in the pathogenesis of the interaction of some neurohormonal mechanisms of the body under toxic stress conditions  [14,s.9;15,s.1-2].   Therefore, the study of the mechanism of interaction between the hypothalamic-pituitary-gonadal system under toxic stress conditions of the body is an urgent issue. We considered it necessary to conduct research in the direction of studying the interaction of neurohormonal mechanisms.

The purpose of the study is to study the role of the arcuate nucleus of the hypothalamus in regulating the interaction between the activities of FSH, PRL, and E2 under normal and toxic stress conditions caused by sulfur dioxide and during post-stress.

MATERIALS AND METHODS

The research work was carried out at the Scientific Research Center of Azerbaijan Medical University and the Department of Normal Physiology. The experiments were conducted on 35 female rabbits weighing 2.5±0.5 kg, with an electrode inserted into the arcuate nucleus of the hypothalamus. The animals were adapted to the experiment 3-4 days before the main experiment. The study was conducted in 7 groups: Group 1 rabbits were in an intact (normal) state; Group 2 for 5 days; Group 3 for 15 days; Group 4 was exposed to a toxic stress model by giving sulfur gas at a dose of 120 PPM in a special chamber for 30 minutes every day for 30 days. Groups 5, 6 and 7 were released for 5, 15 and 30 days after the toxic stress models and were not exposed to any effects. The frequency and amplitude of electroencephalographic (EEG) waves of the arcuate nucleus of the hypothalamus during the toxic stress model and post-model period were recorded using the “Neuro-spectrum-2” (Russia) EEG device. The concentrations of  PRL, FSH and E2 in the blood taken from the ear vein of the rabbit were determined by the immunoenzyme method using special kits. Electron microscopic examination of the ultrastructure of the hypothalamus, pituitary gland and ovary was also performed. The results of this study will be presented in the next scientific works. The obtained indicators were processed in the Microsoft EXCEL-2016 spreadsheet.

RESULTS AND DISCUSSION

Studies have shown that under toxic stress conditions caused by sulfur dioxide, the amplitude and frequency of the EEG waves of the arcuate nucleus of the hypothalamus have changed sharply in different directions compared to normal. After a month of stress, the rhythms of the waves become even more intense. In the post-model period, the rhythms of the EEG waves do not normalize. Toxicity has both an activating and a decelerating effect on the waves compared to normal. Since this effect occurs in the central nervous system, especially in the arcuate nucleus of the hypothalamus, the changes in the adenohypophyseal-gonadal system disrupt the regulatory mechanism of hormones, the activity of FSH, PRL and E2 hormones in the blood changes.

Thus, after the 5th day of toxic stress exposure, the amount of FSH decreases by 32.0%, p<0.001, compared to the norm. In the group released for 5 days after the exposure to the toxic stress model created with sulfur dioxide for 5 days, the absolute value of this quantity decreased sharply compared to the norm, so its relative value decreased insignificantly by 14.0%, p>0.05 (Table 1).

Table 1.

The effect of toxic stress induced by 5-day application of sulfur dioxide to the arcuate nucleus of the hypothalamus and the post-stress period on the concentration of gonadal system hormones in the blood

Note: Reliability compared to the norm - ⁕P >0.05; reliability compared to the norm ⁕⁕P₁  <0.05; reliability compared to the norm ⁕⁕⁕ P₂ <0.001

Since the absolute value of PRL in the blood compared to the normal state increased sharply after the 5th day of the stress model, its relative value was 119.7% (p<0.001). Since the absolute value of PRL in the group released for 5 days after creating the stress model for 5 days was still sharply higher than the norm, its relative value increased by 88.6% (p<0.001) (Table 1).

After the 5th day of toxic stress exposure, the amount of E2 in the blood decreases more than 3 times (68.1%, p <0.001) compared to the normal state. In the group that was released for 5 days after 5 days of stress exposure, the amount of E2 significantly decreased and its level decreased more than 3.0 times (59.1%, p <0.001) (Table 1).

After the 15th day of toxic stress, the decrease in FSH levels continued and its relative decrease compared to the norm was 44.0% p<0.001. In the group released for 15 days after the 15-day stress model, the FSH level increased by 16.0% (p<0.001) (Table 2).

 Table 2.

The effect of toxic stress induced by 15-day application of sulfur dioxide to the arcuate nucleus of the hypothalamus and the post-stress period on the concentration of gonadal system hormones in the blood

Note: Reliability compared to the norm - ⁕P >0.05; reliability compared to the norm ⁕⁕P₁ <0.05; reliability compared to the norm ⁕⁕⁕ P₂ <0.001

On the 15th day of the experiment, the absolute value of PRL in the blood from this effect increased further to 33.2±1.5 pg/ml, and the increase in its relative value was 151.5%,(p <0.001). In the group released for 15 days after creating the 15-day stress model, the absolute value of PRL was 24.7±0.6 ng/ml, and its relative value was 87.1%, (p<0.001) (Table 2). After the 15th day of the stress effect, the amount of E2 decreased by 74.7%, (p<0.001). In the group released for 15 days after 15 days of stress, the amount of E2 decreased by 55.7%, (p<0.001) (Table 2).

After the 30th day of the experiment, the amount of FSH in the blood decreased due to toxic stress, and this decrease was significantly 64.0% (p <0.001) compared to the norm. Slightly different results were obtained for sex steroids. In the group that was released for 30 days after 1 month of stress, the amount of FSH decreased by 16.0% (p <0.05) compared to the norm .

Table 3.

Values

Note: Reliability compared to the norm - ⁕P >0.05; reliability compared to the norm ⁕⁕P₁ <0.05; reliability compared to the norm ⁕⁕⁕ P₂<0.001

The increase in the absolute value of PRL in the blood continued on the 30th day of oxic stress and became even more pronounced. Thus, under the influence of the stress model, the absolute value of this quantity increased to 40.4±1.6 pg/ml, and the relative value was 206.1%. Similarly, such an increase in the amount of PRL in the blood under the influence of toxic stress increased by 131.1%, p<0.05, compared to the norm in animals released in the post-model period (Table 3). fter the 30th day of toxicity, the amount of E2 was 42.5% (p<0.0 01) lower than the norm. In the group that was released for 30 days after the 30-day application of sulfur dioxide, the amount of E2 decreased by 20.0% (p<0.001) compared to the norm (Table 3). As we have noted, toxic stress caused by sulfur dioxide changes the rhythms of the EEG waves of the arcuate nucleus of the hypothalamus. However, since the degree of toxicity in the body increases with the application of sulfur dioxide for a month, the strength of the wave rhythms deepens even more. In the post-model period of toxic stress, no normalization of EEG waves is observed. As we have shown, the realization of stress reactions occurs with the participation of the interaction of the arcuate nucleus, which is one of the integrative centers of the hypothalamus. This neuroendocrine center regulates vital homeostatic parameters and adaptive reactions in normal conditions. A group of biological substances are synthesized in the arcuate nucleus. Also, hypophysiotropic neurons that synthesize the central stress hormone are located in this area of ​​the hypothalamus. Toxic stress disrupts the interaction of hypophysiotropic neurohormonal mechanisms. At the same time, since the monoaminergic and peptidergic structures of the hypothalamus disrupt the regulatory mechanism of the gonadal systems, the synthesis and secretion of pituitary-gonadal hormones into the blood changes [4,s.37;5,s.94;7,s.39;9,s.60; 13,s.155;16,s.590]. Therefore, the changes that occur in the central nervous system, especially in the arcuate nuclei of the hypotha lamus, from this effect alter the activities of the adenohypophyseal-gonadal system hormones in the blood in various directions (Tables 1, 2, 3). Even in the post-model period, the blood activities of these hormones do not normalize. Our results show that under conditions of toxicity caused by sulfur dioxide, the activity of the arcuate nucleus of the hypothalamus changes, resulting in a high feedback loop between FSH, PRL and E2. Meanwhile, there is a positive relationship between FSH and E2. Thus, the arcuate nucleus of the hypothalamus has a complex structure that plays a key role in the regulation of biological functions of the body, and plays an important role in the endocrine regulation of the pituitary-gonadal system. Since toxic stress changes the activity of the arcuate nucleus of the hypothalamus, the synthesis and secretion of hormones into the blood in any link of this system is disrupted. Therefore, in extreme situations, the study of the interaction of the hypothalamic-pituitary-gonadal system and their pathogenetic mechanisms and the discovery of the role of regulatory mechanisms can provide solutions to various theoretical and practical problems. 

CONCLUSION

1. Due to toxic stress and in the post-stress period, the amplitude and frequency rhythms of EEG waves in the arcuate nucleus of the hypothalamus deviate from the norm.

2. Toxicity has both an activating and a decelerating effect on the waves compared to the norm.

3. Since the change in the arcuate nucleus of the hypothalamus due to toxic stress disrupts the regulatory mechanism of the hormones of the adenohypophyseal-gonadal system, the activity of PRL in the blood sharply increases, but the activity of FSH and E2 in the blood decreases.

4. In the post-model period, the activity of hormones does not normalize.

6. The arcuate nucleus of the hypothalamus, in addition to having a complex structure that plays a key role in the regulation of the biological functions of the body, plays an essential role in the endocrine regulation of the adenohypophyseal-gonadal system.

7. In extreme cases, conducting research to study the interaction of the hypothalamic-pituitary-gonadal system and their pathogenetic mechanisms and to identify the role of regulatory mechanisms may allow for the solution of various theoretical and practical issues.

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