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CONCLUSION

Our nervous system is a very complex mechanism, the functioning of which affects the quality of our lives. In turn, the work of all parts of the brain is affected by many aspects, including physical and mental activity and nutrition.

Unfortunately, most of us spend very little time and effort developing our brains and improving our thinking, which does not allow us to make full use of the powerful resources given to us by nature. So, what can you do to optimize brain function? The answer is simple: constantly keep it in good shape, and develop cognitive skills.

Training shall include both logical tasks and tasks provoking an emotional reaction. The range of exercises is very wide: from board games, chess, and puzzles to learning an instrument, writing poetry, and language courses.

In addition, scientists advise traveling more, talking to smart people, establishing interpersonal relationships, and building social bonds.

NEUROTRANSMITTERS AND NEUROPEPTIDES

CHAPTER 6
THE ENDOCRINE SYSTEM

THE "HORMONE" WORD CONCEALS A WHOLE WORLD OF HIDDEN AND OBVIOUS EFFECTS AFFECTING OUR MOOD, AND REACTIONS TO EVENTS, CONTROLLING OUR STATE OF HEALTH, AND KEEPING US YOUNG. EVERY SECOND OUR BODY PRODUCES THOUSANDS OF HORMONE MOLECULES – TINY MESSENGERS THAT HELP THE BODY TO FUNCTION AS A WHOLE. FAILURES OCCURRING IN THIS SYSTEM GRADUALLY LEAD TO ORGAN DYSFUNCTION AND THE DEVELOPMENT OF MANY DISORDERS AND DISEASES.

That is why it is so important to understand how our endocrine system works, what rules it obeys, and how our thoughts, physical activity, diet, sleep, and wakefulness patterns affect it. For example, if we know how chronic stress affects every organ, cell, and molecule, we are much more motivated to overcome negative thoughts, find effective practices to help us cope with stress, and create optimal conditions for maintaining physical and mental health.

HOW DOES THE ENDOCRINE SYSTEM WORK?

The hormone (endocrine) system has a clear hierarchy: there are "controlling" organs and "executing" glands. Hypothalamus is at the top of this hierarchy. This unique structure, located in the diencephalon, combines the properties of neural tissue and gland. Its cells are called neurosecretory cells. In response to a nerve impulse, they fire (like the cells of the nervous system) and start to synthesize hormones (like glandular cells).

The hypothalamus is a powerful "computer" connected to all the structures of the brain and spinal cord. It receives information about the body's internal environment (temperature, energy balance, water, and salt exchange, and blood pressure). And the "wires" coming from organs of senses inform the hypothalamus about events in the external environment. This is where nerve impulses are "translated" into the language of hormones. When the hypothalamus receives information that requires adjustment of the internal environment or behavior, it "turns" to its helper, the pituitary gland.

The pituitary gland, unlike the hypothalamus, does not claim to be the brain but is content with the title of a gland. But not an ordinary one, but the most important one. The pituitary gland is a "messenger" delivering the "decisions" of the hypothalamus to the executing glands. Three groups of hormones are produced in the hypothalamus: liberins, statins, and posterior pituitary lobe hormones. Liberins and statins are regulatory hormones: the former stimulates hormone formation in the pituitary gland and the latter inhibits it. Liberins and statins enter the pituitary gland through small vessels called the portal system and activate or inhibit the production of hormones affecting the body. Oxytocin and vasopressin are the hormones of the posterior pituitary gland. Although both hormones are synthesized in the hypothalamus, they are stored and released by the pituitary gland.

A total of about 15 hormones are synthesized in the pituitary gland. Some of them act directly on a particular gland. For example, thyroid-stimulating hormone stimulates the production of thyroid hormones, and adrenocorticotropic hormone stimulates the synthesis of adrenal hormones. Others have a systemic effect on the entire body.

For example, the somatotropic hormone of the pituitary gland activates bone growth in children and adolescents, affecting the growth sites in the tubular (long) bones, its deficiency is the cause of dwarfism. The somatotropic hormone is also one of the main "builders" of the body, it stimulates protein synthesis in connective tissue, and muscles, which promotes recovery after physical activity, helps to burn fat faster, etc.

The pituitary gland and hypothalamus together form the hypophyseal portal system. The total weight of these organs is barely six grams. Nevertheless, it is the control center not only of our body but also of our emotions, reflexes, potential for longevity, etc.

Hormones synthesized by the pituitary gland under the direction of the hypothalamus are brought with the blood flow to the endocrine glands: thyroid, thymus, pancreas, as well as to ovaries, testicles, and adrenal glands. In response to these hormonal "messages," the glands activate (or block) the production of their hormones, which causes the corresponding physiological effects.

Some pituitary hormones, such as growth (somatotropic) hormone, do without intermediaries – their biological effects are achieved through the direct hormone action on tissues. Other hormones of the pituitary gland, on the other hand, need "levers" to produce results, and the peripheral glands fulfill this role.

The sequential transmission of hormonal signals from the hypothalamus to the pituitary gland and the end gland is called the regulatory axis.

REGULATORY AXIS–PRINCIPLE OF DIRECT AND FEEDBACK

The regulatory axis mechanism can be traced in the example of the interaction between the hypothalamus, pituitary gland, and thyroid gland (hypothalamic pituitary thyroid axis). Regulation is based on the feedback principle, which can be positive or negative. The thyroid gland produces thyroid hormones: triiodothyronine, thyroxin, and calcitonin. They play a key role in the regulation of metabolic processes, in hematopoiesis.

In response to an excessive increase of thyroid hormones in the blood, the pituitary gland stops synthesizing thyroid hormones. As a result, the formation of thyroid hormones stops. This is an example of negative feedback. Conversely, if the level of thyroid hormones decreases, the hypophyseal portal system starts to stimulate their formation. It is positive feedback.

Another hormonal axis of the body, the gonadal-pituitary hypothalamic axis, connects the hypothalamic-pituitary pair with the reproductive organs. It starts with the synthesis of gonadoliberin in the hypothalamus, which, acting on the pituitary gland, stimulates the formation of two other hormones, luteinizing and follicle-stimulating. Targets for these hormones are the reproductive glands: the ovaries in women and the testicles in men. There is a synthesis of sex hormones – estrogen and testosterone. Both hormones are produced in men and women, just in different proportions (the female body has a synthesis of estrogen, and the male body has a synthesis of testosterone).

Different regulatory axes can affect each other. Stressful situations activate the hypothalamic-pituitary-adrenal axis (see details below), which is accompanied by increased formation of the corticoliberin hormone in the pituitary gland. Excess corticoliberin suppresses gonadoliberin synthesis. This leads to lower levels of sex hormones in the body. Therefore, sexual attraction is reduced, and reproductive function is suppressed under stress.

Thus, in the endocrine system, inter-regulation is possible not only between organs but also between entire "hormonal" axes. This gives our body a tremendous opportunity for close "communication" between various organ and tissue systems and causes its adequate reaction to external factors by activating or suppressing the functions of these very organs.

"STRESSAXIS": WHERE DOES THE STRESS COME FROM?

The hypothalamic-pituitary-adrenal axis is called the "stress axis" because it is responsible for the body's response to stressful situations, and its adaptation to changing environmental conditions. On the hypothalamic side, corticoliberin is involved in these processes, which activates the formation of adrenocorticotropic hormone (ACTH) in the pituitary gland. Bloodstream delivers ACTH to the adrenal glands, small paired glands located above the upper pole of the kidneys. They produce glucocorticoids (cortisol) regulating metabolic processes, stress hormones adrenaline, and noradrenaline.

Adrenal hormones are continuously produced in the body and affect different functions. However, their most pronounced effect is the ability to mobilize resources in stressful situations. While adrenaline and noradrenaline are more responsible for sharp stress reactions ("fight-or-flight"), cortisol is called the hormone of long-term or chronic stress.

FUN FACT

CHRONIC STRESS AFFECTS THE BODY AT THE GENETIC LEVEL

Scientists from the Weizmann Institute of Science (Israel) and the Max Planck Institute of Psychiatry (Germany) found that being under chronic stress affects the activity of more than 1,500 genes in body cells.

Experts studied gene expression in nearly 22,000 cells derived from the hypothalamus, pituitary gland, and adrenal cortex of mice. It was found that long-term exposure to stress changed the activity of 66 genes in the hypothalamus, 692 genes in the pituitary gland, and 922 genes in the adrenal glands.

Chronic stress, according to scientists, can affect the entire body and make it more vulnerable to the development of many diseases.

Cortisol in the adrenal glands is synthesized continuously, and its concentration fluctuates throughout the day. The highest level of cortisol is observed in the morning: it helps to move away from sleep, helps maintain energy, regulates blood pressure, and blocks excessive immune system activity (which is important for suppressing inflammation, allergic, and autoimmune reactions). However, in chronic stressful situations, the concentration of this hormone in the blood remains high. Elevated cortisol levels lead to increased anxiety, unease.

Evolutionarily, chronic stress was associated, for example, with food scarcity and "pushed" our ancestors to specific actions (search for food) helping to survive. Today chronic stress is most often caused not by problems of physical survival, but by various troubles at work and in the family, dissatisfaction with the financial situation, reactions to negative news in the media and the Internet, etc. That is, we do not mean stressful situations, which can be "resolved" by clear and specific actions, but constant anxiety, the source of which is mainly in our mind. In turn, elevated cortisol levels lead to increased anxiety and a further increase in the hormone concentration.

So, a vicious circle is formed, forcing us to react to the smallest troubles with an excess of negative, constantly reproducing some stressful events in mind. A consistently high level of cortisol leads to a whole range of unpleasant consequences. These include immune system depression, metabolic disorders leading to diabetes and obesity, hypertension, insomnia, depression, and accelerated aging.

HORMONE PRODUCING CELLS IN THE PERIPHERY

Besides the endocrine cells that make up the "official" glands, there are cells with the same function – hormone production but dispersed throughout the body. Scientists have counted more than 60 types of APUD cells (this is what endocrine-like cells are called), located in different organs. Cells that have hormonal activity but are not part of the "official" endocrine system, scientists called the diffuse neuroendocrine system.

The biggest concentration of hormone-producing cells is in the gastrointestinal tract: stomach, pancreas, large and small intestine. Some hormones (e.g., gastrin, produced by gland cells of the intestine) are mainly engaged in the regulation of digestion. But cholecystokinin, which is synthesized in the duodenum, affects both digestion and human behavior, preventing the development of depression.

The lion's share of serotonin, the hormone of good mood, is produced by the secretory cells of the intestines (60 to 80 % of all serotonin in the body). And in the pancreas, an exact analog of the somatotropic hormone of the pituitary gland is formed, which has the same effect on metabolic processes.

Kidneys, producing renin, have a hormonal "hobby," which raises blood pressure, and erythropoietin, which stimulates blood cell formation. The heart is also not to be immune to hormonal activity: here cardiac atrial natriuretic hormone is synthesized, causing the kidneys to remove sodium faster, and, respectively, water.

And even such an inert substance as adipose tissue also shows hormonal initiative, producing leptin. This hormone increases the sensitivity of cells to insulin (a pancreatic hormone that facilitates glucose penetration into cells). And in high doses (with severe obesity) leptin suppresses insulin formation, which leads to the development of type II diabetes.

EPIPHYSIS: THE GLAND DETERMINING THE COURSE OF OUR LIVES

Epiphysis (or pineal gland) stands apart from the organs of the endocrine system. It is called a "mystery" gland, because this tiny organ weighing less than one gram, located in the center of the brain, has been associated with clairvoyance abilities since antiquity. Modern scientists jokingly call the epiphysis a grey eminence.

As far as researchers know, this gland does not obey the orders of the hormonal "government" – the hypophyseal portal system, but, on the contrary, affects its activity. Due to the epiphysis isolation, and its independence from the influence of the hypophyseal portal system, scientists refer to the pineal gland as the organ of the diffuse neuroendocrine system, just like the hormonal cells of the intestine, kidneys, heart, etc.

The pineal gland consists of nerve cells, glial helper cells, and endocrine pineal cells that synthesize melatonin. Usually, higher levels of melatonin are observed in children, and its amount gradually decreases with age. This curious hormone is currently the subject of many studies. It has been found that it has a multifaceted effect on the body.

It is proved that it helps reduce the risk of cardiovascular disease⁶⁴, regulates the immune system and slows aging⁶⁵, prevents the development of cancer and inhibits the reproduction of tumor cells⁶⁶, helps normalize blood pressure, has a positive effect on metabolic processes, protects against depression and mental disorders⁶⁷. The key function of the epiphysis and its hormone melatonin is the regulation of circadian biorhythms.

REGULATION OF CIRCADIAN BIORHYTHMS

Most of the processes in our body are rhythmic. Every cell of the body is "equipped" with its clock, and our health depends on the proper "running" of all cellular clocks. Some biorhythms are quite independent: the heartbeat and breathing movements are performed with a certain frequency and only to some extent depend on external factors. However, most biorhythms are related to environmental rhythms, also called ecological rhythms.

Biorhythms that last less than a day are called ultradian: they include the rhythm of hormone secretion, alternating periods of vigor and fatigue during the day; the course of metabolic processes causing hunger and satiety, subordinates them.

Infradian rhythms are biorhythms lasting more than a day. Several studies have found that fluctuations in the level of stress hormones in the body (their synthesis, release into the blood, and excretion) correspond to a 21-day cycle⁶⁸. Infradian rhythms include lunar biorhythms, of which the menstrual cycle in women is a good example. During this period, which takes an average of 28 days, the body temperature, blood glucose levels, and the amount of fluid in the body change. There are studies indicating that the full moon increases the number of postoperative hemorrhages and myocardial infarctions⁶⁹.

The most important biorhythms in our lives are circadian (from Latin circadian – "during the day"). The work of hormonal, nervous, respiratory, digestive, cardiovascular, muscular, and immune systems is subject to circadian biorhythms; metabolic processes, tissue repair, physical and mental activity, susceptibility to stress, and much more are connected with circadian rhythms. Epiphysis and its hormone melatonin play a key role in the regulation of all these processes.

FUN FACT

OUR "INTERNAL" DAY IS LONGER THAN THE ASTRONOMICAL ONE

In 1962, French scientist Michel Siffre conducted a chronobiological experiment. Siffre had equipped a cave for a long-term stay with no sunlight. The experimenter's task was to study circadian biorhythms with no access to natural light sources. On July 16, the scientist descended into the cave. Throughout his time in isolation, Siffre notified his colleagues on the outside of his bedtime and waking moments, as well as what time he thought it was. The experiment ended on September 14, but Siffre's subjectively thought that it ended on August 20. It was estimated that even in the absence of natural light sources, the subjective duration of the day (sum of the duration of sleep and wakefulness periods) averaged 24.5 hours. At the same time, the longer the scientist was underground, the longer his subjective day felt. Repeated experiments led by Siffre showed that prolonged isolation (the second time the scientist spent 205 days in a cave) leads to the transition to a 48-hour day (36 hours of wakefulness, 12 hours of sleep).

Although the pineal gland is "hidden" deep in the brain, there is a pathway that allows the epiphysis to "learn" about nights and days and respond to changes in the light regime. How does it happen? Information about the light regime comes from the retina to a structure of the hypothalamus called the suprachiasmatic nucleus (SCN). Then the impulse is sent to the upper cervical sympathetic ganglia and from there it returns to the epiphysis, activating or inhibiting the melatonin production.

During the waking period, light striking the retina supports the activity of thousands of neurons in the suprachiasmatic nucleus. The nerve cells of this hypothalamic department produce a tremendous amount of biologically active substances, including neurotransmitters, hundreds of neuropeptides, cytokines, and various proteins. Most of these substances are related to the regulation of circadian biorhythms in different body cells.

During the night most SCN neurons are inactive, but some nerve cells send impulses to the spinal cord, then return to the epiphysis. Nerve endings that approach the pineal gland release the neurotransmitter noradrenaline, stimulating the melatonin formation in the pineal cells.

In addition, studies show that another neurotransmitter, dopamine, is also involved in melatonin synthesis regulation⁷⁰. Interestingly, dopamine receptors are absent in epiphysis early in the night and only appear closer to the awakening moment. Stimulation of these receptors inhibits melatonin production and makes it easier to wake.

As we age, the function of the suprachiasmatic nucleus as the main "driver" of rhythm decreases. This leads to impaired melatonin formation, sleep problems, and the flattening of many circadian rhythms.

LIGHT REGIME, SLEEP, AND MELATONIN

The human body produces about 30 micrograms of melatonin every 24 hours, and pineal cells synthesize about 70 % of this hormone at night. Melatonin levels start to rise about two hours before bedtime, peaking at an average of 2–3 am, and fall towards 5 am, reaching daytime levels between 7 and 8 am local light time⁷¹.

Sufficient melatonin production in the epiphysis is essential for healthy sleep: it not only determines sleep depth but also takes part in the regulation of sleep phase change. In a study at McGill University (Canada), scientists found two types of melatonin receptors in the brain – MT1, MT2, and MT3⁷².

MT1 receptors are activated during the REM sleep phase, accompanied by eyeball movement. This phase, during which a human dreams, is thought to play a key role in shaping long-term memories.

At the same time, melatonin synthesis is closely linked to the light regime. Bright light in the evening suppresses the production of this hormone, and light from gadgets, and street lighting entering the room during sleep, also negatively affects the melatonin synthesis in the epiphysis.

Besides excessive illumination in the evening, light sources in the room during sleep, sleep and wakefulness disorders, and working at night, other factors negatively affect melatonin formation in the epiphysis. These include a lack of physical activity during the day, chronic stress, and excessive caloric intake.

WHAT ARE THE CONSEQUENCES OF SLEEP DISORDERS AND MELATONIN DEFICIENCY?

Insufficient formation of melatonin in the epiphysis leads to several negative consequences, including an increased risk of cancer. A group of American scientists from the University of Texas found that people who live in regions with high levels of street artificial lighting at night have an increased risk of thyroid cancer⁷³.

According to the study, residents in areas with the highest nighttime light levels had a 55 % higher risk of this type of cancer than residents in low-light areas. Moreover, this connection was more pronounced in women. According to the report, this situation stems from the fact that the level of the female sex hormone estrogen increases due to melatonin deficiency, which creates conditions for cancer development. In addition, according to experts, malfunctions of the body's internal clock due to insufficient formation of melatonin is a favorable background for the emergence and multiplication of cancer cells.

Night work is another danger to health. A study conducted by scientists at Washington State University (USA) showed that disruption of circadian rhythms due to such a regimen increases the risk of DNA breaks and cancer development⁷⁴.

Lab results proved that the night shift altered the normal circadian rhythmicity of genes associated with the development of cancer. It turned out that the volunteers with the night schedule had significantly more breaks in the DNA structure than the control group. Moreover, the former demonstrated a strong vulnerability of blood cells to radiation-induced DNA damage.

Other negative effects of melatonin deficiency associated with sleep and wakefulness disorders include accelerated aging, immune suppression, increased risk of metabolic disorders (diabetes, obesity), hypertension, Alzheimer's, and Parkinson's diseases⁷⁵.

HOW TO SLEEP TO MAINTAIN MELATONIN FORMATION IN THE RIGHT AMOUNT?

A few rules can help ensure optimal conditions for melatonin formation during sleep.

1. Train yourself to go to bed and get up at the same time, try to stick to this regime not only on weekdays but also on weekends.

2. Hung black-out curtains over the windows of the bedroom, so they do not let light in.

3. Do not watch TV and stop using gadgets at least one hour before bedtime.

4. Do not smoke or drink alcohol at least four hours before bedtime.

5. Evening meditation will help to reduce stress hormones, calm the brain, and put it to sleep.

6. Avoid eating junk foods in the evening, as well as foods rich in spices. Include complex carbohydrates in your dinner, such as cereal, and vegetable salads.

7. Take a warm bath shortly before bedtime.

8. Move more throughout the day: aerobic exercises and yoga in the morning and daylight help you fall asleep faster in the evening.

FUN FACT

REM SLEEP PLAYS AN IMPORTANT ROLE IN LIFE EXTENSION

Experts from Stanford University have found that REM sleep is important not only for memory and other cognitive functions of the brain but also for life expectancy. The study found that problems with REM sleep increase the risk of early death from all causes: reducing REM sleep by just 5 % increased the risk of premature death by 13 %. The experts noted that the reduction in the duration of REM by 15 % is particularly dangerous.