Hormones of the adrenal medulla, catecholamines. Catecholamines and their action

Some human hormones and the connection of the endocrine system with the nervous system are shown in Fig. 13.2. Under the direct control of the nervous system are the adrenal medulla and the hypothalamus; other endocrine glands are connected with the nervous system indirectly, through the hormones of the hypothalamus and pituitary gland. In the cells of the hypothalamus, special peptides are synthesized - liberins (releasing hormones). In response to the excitation of certain centers of the brain, liberins are released from the axons of the hypothalamic nerve cells, ending in the pituitary gland, and stimulate the synthesis and release of tropic hormones by the pituitary cells. Along with liberins, statins are produced in the hypothalamus, which inhibit the synthesis and secretion of pituitary hormones.

central nervous system

N erv e connections

N erv e ties ___
	Hypothalamus		Antidiure-
			Antidiure-
			tic

			Oxytocype		uterine muscles,
			Oxytocype		mammary glands
			Melanocyte-
			stimulate-		melanocytes
			ing hormone
			Prolactia		Milk glands
Somatotropin
			Lutsinizi-		Folliculo-
	Corticotropin	Thyrotropin		stimulating
	Corticotropin	Thyrotropin

Brain		Thyroid			testicles
substance		Thyroid
substance	adrenal glands
adrenal glands	adrenal glands
ADRENALIN	CORTISOL	THIROXINE ESTROGEN			ANDROGENS

Rice. 13.2. Connections between the endocrine and nervous systems. Solid arrows indicate the synthesis and secretion of the hormone, dotted arrows indicate the effect of the hormone on target organs.

The classification of hormones according to biological functions is to a certain extent conditional, since many hormones are polyfunctional. For example, epinephrine and noradrenaline regulate not only carbohydrate and fat metabolism, but also heart rate, smooth muscle contraction, and blood pressure. In particular, for this reason, many hormones, especially paracrine ones, cannot be classified according to biological functions.

Changes in the concentration of hormones in the blood

The concentration of hormones in the blood is low, of the order of IO6-IO JJ mol / l. The half-life in the blood is measured in minutes, for some hormones - tens of minutes, less often - hours. An increase in the concentration of a hormone in the blood under the action of an appropriate stimulus depends on an increase in the rate of hormone synthesis or the rate of secretion of a hormone already present in the endocrine cell.

Steroid hormones are lipophilic substances that easily penetrate cell membranes. Therefore, they do not accumulate in cells, and an increase in their concentration in the blood is determined by an increase in the rate of synthesis.

Peptide hormones are secreted into the blood with the participation of special mechanisms of secretion. These hormones after their synthesis are included in the secretory granules - membrane vesicles formed in the lamellar complex; The hormone is released into the blood by the fusion of the granule with the plasma membrane of the cell (exocytosis). The synthesis of hormones occurs quickly (for example, a proinsulin molecule is synthesized in 1-2 minutes), while the formation and maturation of secretory granules require more time - 1-2 hours. The storage of the hormone in secretory granules ensures a quick response of the body to the action of a stimulus : the stimulus accelerates the fusion of the granules with the membrane and the release of the stored hormone into the blood.

Synthesis of steroid hormones

The structure and synthesis of many hormones are described in the previous sections. Steroid hormones are a group of compounds related in origin and structure: they are all formed from cholesterol. Intermediate products in the synthesis of steroid hormones are pregnenolone and progesterone (Fig. 13.3). They are formed in all organs that synthesize any steroid hormones. Further transformation paths diverge: in the adrenal cortex, cortisol (glucocorticosteroid) and aldosterone (mineralocorticosteroid) (C-steroids) are formed, in the testes - male sex hormones (C19-steroids), in the ovaries - female sex hormones (C18-steroids) . Most of the arrows in the diagram hide not one, but two to four reactions. In addition, alternative pathways for the synthesis of some hormones are possible. In general, the pathways for the synthesis of steroid hormones form a rather complex network of reactions. Many intermediates in these pathways also have some hormonal activity. However, the main steroid hormones are cortisol (regulation of carbohydrate and amino acid metabolism), aldosterone (regulation of water-salt metabolism), testosterone, estradiol, and progesterone (regulation of reproductive functions).

As a result of inactivation and catabolism of steroid hormones, a significant amount of steroids containing a keto group in position 17 (17-ketosteroids) is formed. These substances are excreted through the kidneys. The daily excretion of 17-ketosteroids in an adult woman is 5-15 mg, in men - 10-25 mg. The determination of 17-ketosteroids in urine is used for diagnosis: their excretion increases in diseases accompanied by hyperproduction of steroid hormones, and decreases with hypoproduction.

Progesterone (C21) Aldosterone (C21)

Rice. 13.3. Ways of synthesis of steroid hormones:

1,2 - in the adrenal cortex, testes and ovaries; 3, 4 - in the adrenal cortex; 5 - in the testes and ovaries; 6 - in the ovaries

paracrine hormones

Cytokines

Cytokines are signaling molecules of paracrine and autocrine action; in the blood in a physiologically active concentration, they practically do not exist (an exception is interleukin-1). Dozens of different cytokines are known. These include interleukins (lymphokines and monokines), interferons, peptide growth factors, colony stimulating factors. Cytokines are glycoproteins containing 100-200 amino acid residues. Most cytokines are formed and act in many cell types and respond to various stimuli, including mechanical damage, viral infection, metabolic disorders, etc. The exception is interleukins (IL-1a and IL-1R) - their synthesis is regulated by specific signals and in a small number of cell types.

Cytokines act on cells through specific membrane receptors and protein kinase cascades, as a result, transcription factors are activated - enhancers or silencers, proteins that are transported to the cell nucleus find a specific DNA sequence in the promoter of the gene that is the target of this cytokine, and activate or suppress gene transcription .

Cytokines are involved in the regulation of proliferation, differentiation, chemotaxis, secretion, apoptosis, and inflammation. Transforming growth factor (TGF-r) stimulates the synthesis and secretion of extracellular matrix components, cell growth and proliferation, and the synthesis of other cytokines.

Cytokines have overlapping yet distinct biological activities. Cells of different types, or different degrees of differentiation, or in different functional states may respond differently to the same cytokine.

Eicosanoids

Arachidonic acid, or eicosatetraenoic acid, 20:4 (5, 8, 11, 14), gives rise to a large group of paracrine hormones - eicosanoids. Arachidonic acid, supplied with food or formed from linoleic acid, is included in the composition of membrane phospholipids and can be released from them as a result of the action of phospholipase A .. Further, eicosanoids are formed in the cytosol (Fig. 13.4). There are three groups of eicosanoids: prostaglandins (PG), thromboxanes (TX), leukotrienes (LT). Eicosanoids are produced in very small quantities, and usually have a short lifetime - measured in minutes or even seconds.

Leukotrienes

Rice. 13.4. Synthesis and structure of some eicosanoids:

1 - phospholipase A2; 2 - cyclooxygenase

In different tissues and different situations, unequal eicosanoids are formed. The functions of eicosanoids are diverse. They cause smooth muscle contraction and vasoconstriction (PGF2Ct, synthesized in almost all organs) or, conversely, smooth muscle relaxation and vasodilation (PGE2, also synthesized in most organs). PGI2 is synthesized mainly in the vascular endothelium, inhibits platelet aggregation, dilates blood vessels. Thromboxane TXA2 is synthesized mainly in platelets and also acts on platelets - it stimulates their aggregation (autocrine mechanism) in the area of vessel damage (see Chapter 21). It, thromboxane TXA2, constricts blood vessels and bronchi, acting on smooth muscle cells (paracrine mechanism).

Eicosanoids act on target cells through specific membrane receptors. The binding of an eicosanoid to a receptor triggers the formation of a second (intracellular) signal messenger; they can be cAMP, cGMP, inositol trisphosphate, Ca2+ ions. Eicosanoids, along with other factors (histamine, interleukin-1, thrombin, etc.), are involved in the development of the inflammatory response.

Inflammation is a natural response to tissue damage, the initial link in healing. However, sometimes inflammation is excessive or too long, and then it itself becomes a pathological process, a disease, and requires treatment. Inhibitors of eicosanoid synthesis are used to treat such conditions. Cortisol and its synthetic analogues (dexamethasone and others) induce the synthesis of lipocortin proteins, which inhibit phospholipase A2 (see Fig. 13.4). Aspirin (non-steroidal anti-inflammatory drug) acetylates and inactivates cyclooxygenase (Fig. 13.6).

Rice. 13.6. Inactivation of cyclooxygenase by aspirin

Catecholamine hormones - dopamine, norepinephrine and adrenaline - are 3,4-dihydroxy derivatives of phenylethylamine. They are synthesized in the chromaffin cells of the adrenal medulla. These cells got their name because they contain granules that stain red-brown under the action of potassium dichromate. Clusters of such cells have also been found in the heart, liver, kidneys, gonads, adrenergic neurons of the postganglionic sympathetic system, and in the central nervous system.

The main product of the adrenal medulla is adrenaline. This compound accounts for approximately 80% of all medulla catecholamines. Outside the medulla, adrenaline is not formed. In contrast, norepinephrine, found in organs innervated by sympathetic nerves, is formed predominantly in situ (~ 80% of the total); the rest of norepinephrine is also formed mainly at the nerve endings and reaches its targets in the blood.

The conversion of tyrosine to adrenaline involves four successive steps: 1) ring hydroxylation, 2) decarboxylation, 3) side chain hydroxylation, and 4) N-methylation. The catecholamine biosynthesis pathway and the enzymes involved are shown in Fig. 49.1 and 49.2.

Tyrosine - hydroxylase

Tyrosine is the direct precursor of catecholamines, and tyrosine hydroxylase limits the rate of the entire process of catecholamine biosynthesis. This enzyme occurs both in free form and in the form associated with subcellular particles. With tetrahydropteridine as a cofactor, it performs an oxidoreductase function, converting L-tyrosine to L-dihydroxyphenylalanine (-DOPA). There are various ways to regulate tyrosine hydroxylase as a rate-limiting enzyme. The most important of these is the feedback inhibition by catecholamines: catecholamines compete with the enzyme for the pteridine cofactor, forming a Schiff base with the latter. Tyrosine hydroxylase is also competitively inhibited by a number of tyrosine derivatives, including α-methyltyrosine. In some cases, this compound is used to block the excess production of catecholamines in pheochromocytoma, but there are more effective agents that also have less pronounced side effects. Compounds of another group inhibit the activity of tyrosine hydroxylase by forming complexes with iron and thus removing the existing cofactor. An example of such a compound is α,-dipyridyl.

Catecholamines do not cross the blood-brain barrier and hence their presence in the brain must be explained by local synthesis. In some diseases of the central nervous system, such as Parkinson's disease, there are violations of the synthesis of dopamine in the brain. dopamine precursor

Rice. 49.1. biosynthesis of catecholamines. ONMT - phenylethanolamine-N-methyltransferase. (Modified and reproduced, with permission, from Goldfien A. The adrenal medulla. In: Basic and Clinical Endocrinology, 2nd ed. Greenspan FS, Forsham PH . Appleton and Lange, 1986.)

FA - easily overcomes the blood-brain barrier and therefore serves as an effective treatment for Parkinson's disease.

DOPA decarboxylase

Unlike tyrosine hydroxylase. found only in tissues capable of synthesizing catecholamines, DOPA decarboxylase is present in all tissues. This soluble enzyme requires pyridoxal phosphate to convert α-DOPA to α-dihydroxyphenylethylamine (dopamine). The reaction is competitively inhibited by compounds resembling α-DOPA, such as a-methyl-DOPA. Halogenated compounds form a Schiff base with α-DOPA and also inhibit the decarboxylation reaction.

α-methyl-DOPA and other related compounds such as α-hydroxytyramine (derived from tyramine), α-methyl irosin and metaraminol have been successfully used to treat some forms of hypertension. The antihypertensive effect of these metabolites is apparently due to their ability to stimulate a-adrenergic receptors (see below) of the corticobulbar system in the central nervous system, which leads to a decrease in the activity of peripheral sympathetic nerves and a decrease in blood pressure.

Dopamine-b-hydroxylase

Dopamine-b-hydroxylase (DBH) is a mixed-function oxidase that catalyzes the conversion of dopamine to norepinephrine. DBG uses ascorbate as an electron donor and fumarate as a modulator; the active center of the enzyme contains copper. DBH cells of the adrenal medulla are probably localized in secretory granules. Thus, the conversion of dopamine to norepinephrine occurs in these organelles. DBH is released from the cells of the adrenal medulla and nerve endings along with norepinephrine, but (unlike the latter) is not reuptaken by the nerve endings.

Phenylethanolamine-N-methyltransferase

Soluble enzyme phenylethanolamine - α-methyltransferase (FCMT) catalyzes β-methylation of norepinephrine with the formation of adrenaline in adrenaline-producing cells of the adrenal medulla. Since this enzyme is soluble, it can be assumed that the conversion of noradrenaline to adrenaline occurs in the cytoplasm. Synthesis of FIMT is stimulated by glucocorticoid hormones that penetrate into the medulla through the intraadrenal portal system. This system provides 100 times greater concentration of steroids in the medulla than in systemic arterial blood. Such a high concentration in the adrenal glands, apparently, is necessary for the induction

Catecholamines are physiologically active substances that can be presented both as mediators and as hormones. They are very important in the control and molecular interaction between cells in humans and animals. Catecholamines are produced by synthesis in the adrenal glands, more precisely, in their medulla.

All higher human activity associated with the functioning and activity of nerve cells is carried out with the help of these substances, since neurons use them as intermediaries (neurotransmitters) that transmit a nerve impulse. Not only physical, but also mental endurance, depend on the exchange of catecholamine in the body. For example, not only the speed of thinking, but also its quality depends on the quality of the metabolic processes of these substances.

The mood of a person, the speed and quality of memorization, the reaction of aggression, emotions and the general energy tone of the body depend on how actively catecholamine is synthesized and used in the body. Also, catecholamines trigger the processes of oxidation and reduction in the body (carbohydrates, proteins and fats), which release the energy necessary to feed the nerve cells.

In sufficiently large quantities, catecholamines are found in children. That is why they are more mobile, emotionally saturated and trainable. However, with age, their number significantly decreases, which is associated with a decrease in the synthesis of catecholamines both in the central nervous system and in the peripheral one. This is associated with a slowdown in thought processes, memory impairment and a decrease in mood.

Now catecholamines include four substances, three of which are brain neurotransmitters. The first substance is a hormone, but not a mediator, and is called serotonin. Found in platelets. The synthesis and storage of this substance occurs in the cellular structures of the gastrointestinal tract. It is from there that it is transported into the blood and further, under its control, the synthesis of biologically active substances occurs.

If its blood levels are increased by 5 to 10 times, then this may indicate the formation of tumors of the lungs, intestines or stomach. At the same time, in the analysis of urine, the indicators of the decay products of serotonin will be significantly increased. After surgery and elimination of the tumor, these indicators in blood plasma and urine return to normal. Their further study helps to exclude a possible recurrence or the formation of metastases.

Less possible causes of an increase in the concentration of serotonin in the blood and urine are acute myocardial infarction, thyroid cancer, acute intestinal obstruction, etc. A decrease in the concentration of serotonin is also possible, which indicates Down syndrome, leukemia, hypovitaminosis B6, etc.

Dopamine is the second hormone from the catecholamine group. Neurotransmitter of the brain, synthesized in special neurons of the brain, which are responsible for the regulation of its main functions. It stimulates the release of blood from the heart, improves blood flow, dilates blood vessels, etc. With the help of dopamine, the glucose content in human blood increases, due to the fact that it prevents its utilization, while simultaneously stimulating the process of glycogen breakdown.

Regulatory function in the formation of human growth hormone is also important. If an increased content of dopamine is observed in the analysis of urine, then this may indicate the presence of a hormonally active tumor in the body. If the indicators are lowered, then the motor function of the body is disturbed (Parkinson's syndrome).

An equally important hormone is norepinephrine. It is also a neurotransmitter in the human body. It is synthesized by the cells of the adrenal glands, the endings of the synoptic nervous system and the cells of the central nervous system from dopamine. Its amount in the blood increases in a state of stress, large physical. loads, bleeding and other situations that require immediate response and adaptation to new conditions.

It has a vasoconstrictive effect and mainly affects the intensity (velocity, volume) of blood flow. Very often, this hormone is associated with rage, since when it is released into the bloodstream, an aggression reaction occurs and muscle strength increases. The face of an aggressive person turns red precisely due to the release of norepinephrine.

Adrenaline is a very important neurotransmitter in the body. The main hormone contained in the adrenal glands (their medulla) and synthesized there from norepinephrine.

Associated with the reaction of fear, since with a sharp fright, its concentration increases sharply. As a result, the heart rate increases, blood pressure increases, coronary blood flow increases, and glucose concentration increases.

It also causes vasoconstriction of the skin, mucous membranes and abdominal organs. In this case, the person's face may noticeably turn pale. Adrenaline increases the stamina of a person who is in a state of excitement or fear. This substance is like an important dope for the body and therefore, the greater its amount in the adrenal glands, the more active a person is physically and mentally.

Study of the level of catecholamines

Currently, the result of a test for catecholamines is an important indicator of the presence of tumors or other serious diseases of the body. To study the concentration of catecholamines in the human body, two main methods are used:

Catecholamines in blood plasma. This research method is the least popular, since the removal of these hormones from the blood occurs instantly, and an accurate study is possible only when it is taken at the time of acute complications (for example, a hypertensive crisis). As a result, it is extremely difficult to carry out such a study in practice.
Urinalysis for catecholamines. In a urinalysis, hormones 2, 3 and 4 are examined in our list presented earlier. As a rule, daily urine is examined, and not a one-time delivery, since within one day a person may be subject to stressful situations, fatigue, heat, cold, physical. loads, etc., which provokes the release of hormones and contributes to obtaining more detailed information. The study includes not only the determination of the level of catecholamines, but also their metabolites, which significantly increases the accuracy of the results. This study should be taken seriously and all factors that distort the results (caffeine, adrenaline, exercise and stress, ethanol, nicotine, various drugs, chocolate, bananas, dairy products) should be excluded.

Many external factors can influence these results of the study. Therefore, in combination with analyzes, an important place is occupied by the physical and emotional state of the patient, what medicines he takes and what he eats. When undesirable factors are eliminated, the study is repeated in order to accurately diagnose.

Although tests for the concentration of catecholamines in the human body can help in detecting a tumor, they, unfortunately, are unable to show the exact place of origin and its nature (benign or malignant). They also do not show the number of tumors formed.

Catecholamines are indispensable substances for our body. Thanks to their presence, we can cope with stress, physical overload, increase our physical, mental and emotional activity. Their indicators will always warn us of dangerous tumors or diseases. In response, it is only necessary to pay enough attention to them and to investigate their concentration in the body in a timely and responsible manner.

The effects of catecholamines begin with interaction with specific receptors on target cells. While the receptors for thyroid and steroid hormones are localized inside the cells, the receptors for catecholamines (as well as for acetylcholine and peptide hormones) are present on the outer cell surface.

It has long been established that for some reactions, epinephrine or norepinephrine are more effective than the synthetic catecholamine isoproterenol, while for others, the effect of isoproterenol is superior to that of adrenaline or norepinephrine. On this basis, the concept was developed that there are two types of adrenoreceptors in tissues: a and B, and in some of them only one of these two types can be present.

Isoproterenol is the most potent β-adrenergic agonist, while the synthetic compound phenylephrine is the most potent α-adrenergic agonist. Natural catecholamines - epinephrine and norepinephrine - are able to interact with both types of receptors, however, adrenaline shows a greater affinity for β-, and norepinephrine - for a-receptors. Catecholamines activate cardiac β-adrenergic receptors more strongly than smooth muscle β-receptors, which made it possible to subdivide the β-type into subtypes: β1-receptors (heart, fat cells) and β2-receptors (bronchi, blood vessels, etc.). The action of isoproterenol on β1-receptors exceeds the action of adrenaline and noradrenaline only 10 times, while it acts on β2-receptors 100-1000 times stronger than natural catecholamines.

The use of specific antagonists (phentolamine and phenoxybenzamine for α- and propranolol for β-receptors) confirmed the adequacy of the classification of adrenergic receptors. Dopamine is able to interact with both a- and b-receptors, but in various tissues (brain, pituitary gland, blood vessels) its own dopaminergic receptors have also been found, the specific blocker of which is haloperidol. The number of β receptors ranges from 1000 to 2000 per cell.

The biological effects of catecholamines, mediated by β-receptors, are usually associated with the activation of adenylate cyclase and an increase in the intracellular content of cAMP. The receptor and the enzyme, although functionally connected, are different macromolecules. Guanosine triphosphate (GTP) and other purine nucleotides take part in the modulation of adenylate cyclase activity under the influence of the hormone receptor complex. By increasing the activity of the enzyme, they appear to decrease the affinity of the β receptors for agonists.

The phenomenon of increasing the sensitivity of denervated structures has long been known. Conversely, long-term exposure to agonists reduces the sensitivity of target tissues. The study of β-receptors made it possible to explain these phenomena.

It has been shown that long-term exposure to isoproterenol leads to a loss of adenylate cyclase sensitivity due to a decrease in the number of β-receptors. The process of desensitization does not require the activation of protein synthesis and is probably due to the gradual formation of irreversible hormone-receptor complexes. On the contrary, the introduction of 6-oxidopamine, which destroys sympathetic endings, is accompanied by an increase in the number of responsive β-receptors in tissues. It is possible that an increase in sympathetic nervous activity also causes age-related desensitization of blood vessels and adipose tissue in relation to catecholamines.

The number of adrenoreceptors in different organs can be controlled by other hormones. So, estradiol increases, and progesterone reduces the number of a-adrenergic receptors in the uterus, which is accompanied by a corresponding increase and decrease in its contractile response to catecholamines. If the intracellular "second messenger", formed under the action of β-receptor agonists, is certainly cAMP, then with regard to the transmitter of α-adrenergic influences, the situation is more complicated. The existence of various mechanisms is assumed: a decrease in the level of cAMP, an increase in the content of cAMP, modulation of cellular calcium dynamics, etc.

To reproduce a variety of effects in the body, doses of epinephrine are usually required, 5-10 times smaller than norepinephrine. Although the latter is more effective at both α- and β1-adrenergic receptors, it is important to remember that both endogenous catecholamines are able to interact with both α- and β-receptors. Therefore, the biological response of a given organ to adrenergic activation largely depends on the type of receptors present in it. However, this does not mean that selective activation of the nervous or humoral link of the sympathetic-adrenal system is impossible. In most cases, there is an increased activity of its various links. Thus, it is generally accepted that hypoglycemia reflexively activates the adrenal medulla, while a decrease in blood pressure (postural hypotension) is mainly accompanied by the release of norepinephrine from the endings of sympathetic nerves.

In table. 24 shows selective data characterizing the type of adrenoreceptors in various tissues and the biological reactions mediated by them.

Table 24. Adrenoreceptors and the effects of their activation in various tissues

It is important to consider that the results of intravenous administration of catecholamines do not always adequately reflect the effects of endogenous compounds. This applies mainly to norepinephrine, since in the body it is released mainly not into the blood, but directly into the synaptic clefts. Therefore, endogenous norepinephrine activates, for example, not only vascular α-receptors (increased blood pressure), but also β-receptors of the heart (increased heart rate), while the introduction of norepinephrine from the outside leads mainly to the activation of vascular α-receptors and reflex (through the vagus) slowing down heartbeats.

Low doses of epinephrine activate mainly β-receptors in muscle vessels and the heart, resulting in a decrease in peripheral vascular resistance and an increase in cardiac output. In some cases, the first effect may predominate, and hypotension develops after the administration of epinephrine. In higher doses, adrenaline also activates a-receptors, which is accompanied by an increase in peripheral vascular resistance and, against the background of an increase in cardiac output, leads to an increase in blood pressure.

However, its effect on vascular β-receptors also remains. As a result, the increase in systolic pressure exceeds that of diastolic pressure (an increase in pulse pressure). With the introduction of even larger doses, the a-mimetic effects of adrenaline begin to predominate: systolic and diastolic pressure increase in parallel, as under the influence of norepinephrine.

The effect of catecholamines on metabolism consists of their direct and indirect effects. The former are realized mainly through β-receptors. More complex processes are associated with the liver. Although an increase in hepatic glycogenolysis is traditionally considered to be the result of activation of β-receptors, there is evidence that α-receptors are also involved in this.

The mediated effects of catecholamines are associated with the modulation of the secretion of many other hormones, such as insulin. In the action of adrenaline on its secretion, the α-adrenergic component clearly predominates, since it has been shown that any stress is accompanied by inhibition of insulin secretion. The combination of direct and indirect effects of catecholamines causes hyperglycemia, associated not only with an increase in hepatic glucose production, but also with inhibition of its utilization by peripheral tissues. The acceleration of lipolysis causes hyperlipacidemia with increased delivery of fatty acids to the liver and intensification of the production of ketone bodies. Increased glycolysis in the muscles leads to an increase in the release of lactate and pyruvate into the blood, which, together with glycerol released from adipose tissue, serve as precursors of hepatic gluconeogenesis.

Regulation of catecholamine secretion

The similarity of the products and methods of response of the sympathetic nervous system and the adrenal medulla was the basis for combining these structures into a single sympathetic-adrenal system of the body with the release of its nervous and hormonal links. Various afferent signals are concentrated in the hypothalamus and the centers of the spinal and medulla oblongata, from where efferent messages originate, switching to the cell bodies of preganglionic neurons located in the lateral horns of the spinal cord at the level of the VIII cervical - II-III lumbar segments.

The preganglionic axons of these cells leave the spinal cord and form synaptic connections with neurons located in the ganglia of the sympathetic chain or with cells of the adrenal medulla. These preganglionic fibers are cholinergic. The first fundamental difference between sympathetic postganglionic neurons and chromaffin cells of the adrenal medulla is that the latter transmit the cholinergic signal that comes to them not by nerve conduction (postganglionic adrenergic nerves), but by the humoral pathway, releasing adrenergic compounds into the blood. The second difference is that the postganglionic nerves produce norepinephrine, while the cells of the adrenal medulla produce predominantly adrenaline. These two substances have different effects on tissues.

Phenylethylamines or catecholamines - what is it? These are active substances that act as intermediaries in intercellular chemical interactions in the human body. These include: norepinephrine (norepinephrine), which are hormonal substances, as well as dopamine, which is a neurotransmitter.

general information

Catecholamines - what is it? These are several hormones that are produced in the adrenal glands, its medulla, and enter the bloodstream as a response to an emotional or physical stressful situation. Further, these active substances take part in the transmission of nerve impulses to the brain, provoke:

release of energy sources, which are fatty acids and glucose;
dilated pupils and bronchioles.

Norepinephrine directly raises blood pressure by constricting blood vessels. Adrenaline acts as a metabolic stimulant and increases the heart rate. After the hormonal substances do their job, they break down and are excreted from the body along with urine. Thus, the functions of catecholamines are that they provoke the endocrine glands to work actively, and also contribute to the stimulation of the pituitary and hypothalamus. Normally, the amount of catecholamines and their metabolites is contained in small amounts. However, under stress, their concentration increases for some time. In some pathological conditions (chromaffin tumors, neuroendocrine tumors), a huge amount of these active substances is formed. Analyzes can detect them in the blood and urine. In this case, the following symptoms appear:

increased blood pressure for a short or long period;
very severe headaches;
trembling in the body;
increased sweating;
prolonged anxiety;
nausea;
slight tingling in the limbs.

An effective method of treating tumors is surgical intervention aimed at its removal. As a result, catecholamine levels decrease and symptoms decrease or disappear.

Mechanism of action

The effect is to activate membrane receptors located in the cell tissue of target organs. Further, protein molecules, changing, trigger intracellular reactions, due to which a physiological response is formed. Hormonal substances produced by the adrenal glands and the thyroid gland increase the sensitivity of receptors to norepinephrine and adrenaline.

These hormonal substances affect the following activities of the brain:

aggressiveness;
mood;
emotional stability;
reproduction and assimilation of information;
speed of thinking;
are involved in shaping behavior.

In addition, catecholamines provide energy to the body. A high concentration of this complex of hormones in children leads to their mobility, cheerfulness. As they grow older, the production of catecholamines decreases, and the child becomes more restrained, the intensity of mental activity decreases somewhat, possibly a worsening of mood. By stimulating the hypothalamus and pituitary gland, catecholamines increase the activity of the endocrine glands. Intense physical or mental stress, in which the heart rate increases and body temperature rises, leads to an increase in catecholamines in the blood stream. The complex of these active substances acts rapidly.

Types of catecholamines

Catecholamines - what is it? These are biologically active substances, which, due to their instant response, allow the individual's body to work ahead of schedule.

Norepinephrine. This substance has a different name - the hormone of aggression or rage, as it gets into the bloodstream, provokes irritability and an increase in muscle mass. The amount of this substance is directly related to great physical overload, stressful situations or allergic reactions. Excess norepinephrine, having a narrowing effect on the vessels, has a direct effect on the rate of circulation and blood volume. The person's face takes on a red tint.
Adrenalin. The second name is the hormone of fear. Its concentration increases with excessive experiences, stress, both physical and mental, as well as with a strong fright. This hormonal substance is formed from norepinephrine and dopamine. Adrenaline, by constricting blood vessels, provokes an increase in pressure and affects the rapid breakdown of carbohydrates, oxygen and fats. The face of the individual takes on a pale appearance, endurance with strong excitement or fright increases.
Dopamine. The hormone of happiness is called this active substance, which is involved in the production of norepinephrine and adrenaline. It has a vasoconstrictive effect on the body, provokes an increase in the concentration of glucose in the blood, suppressing its utilization. It inhibits the production of prolactin, and affects the synthesis of growth hormone. Dopamine affects sexual desire, sleep, thought processes, joy, and the pleasure of eating. An increase in the excretion of dopamine from the body along with urine is found in the presence of tumors of a hormonal nature. In brain tissues, the level of this substance increases with a lack of pyridoxine hydrochloride.

Biological action of catecholamines

Adrenaline significantly affects cardiac activity: it enhances conductivity, excitability and contractility of the myocardial muscle. Under the influence of this substance, blood pressure rises, and also increases:

strength and heart rate;
minute and systolic blood volume.

Excess concentration of adrenaline can provoke:

arrhythmia;
in rare cases, ventricular fibrillation;
violation of oxidation processes in the heart muscle;
changes in metabolic processes in the myocardium, up to dystrophic changes.

Unlike epinephrine, noradrenaline does not significantly affect cardiac activity and causes a decrease in heart rate.

Both hormones:

They have a vasoconstrictive effect on the skin, lungs and spleen. In adrenaline, this process is more pronounced.
Expand the coronary arteries of the stomach and heart, while the effect of norepinephrine on the coronary arteries is stronger.
They play a role in the metabolic processes of the body. Adrenaline dominates.
They help to reduce the tone of the muscles of the gallbladder, uterus, bronchi, intestines. Norepinephrine is less active in this case.
They cause a decrease in eosinophils and an increase in neutrophils in the blood.

In what cases is a urine test prescribed?

An analysis of catecholamines in the urine makes it possible to identify disorders that, due to pathological processes, lead to disruption of the normal functioning of the body. Failures can be caused by various serious diseases. Assign this type of laboratory research in the following cases:

To control therapy in the treatment of chromaffin tumor.
With a neuroendocrine or identified neoplasm of the adrenal glands, or a genetic predisposition to tumor formation.
With hypertension, which is not treatable.
The presence of hypertension with persistent headache, palpitations and increased sweating.
Suspicion of a chromaffin neoplasm.

Preparing for a urine test

The determination of catecholamines helps to confirm the presence of pathological processes in the human body, such as high blood pressure and oncology, as well as to verify the effectiveness of the treatment of pheochromocytoma and neuroblastoma. For accurate results of the analysis, you should undergo training, which consists of the following:

Two weeks before the procedure, do not take drugs that affect the increased release of norepinephrine from the endings of the adrenergic nerves, in agreement with the attending doctor.
For two days, do not drink drugs that have a diuretic effect. Exclude tea, coffee, alcohol-containing drinks, cocoa, beer, as well as cheese, avocados and other exotic vegetables and fruits, all legumes, nuts, chocolate, all products that contain vanillin.
For a day and during the collection of daily urine, avoid any overvoltage, exclude smoking.

Immediately before collecting urine for analysis for catecholamines, perform genital hygiene. Biological material is collected three times a day. Do not take the first morning portion. Three hours after that, urine is taken, the second time - after six and further, after 12 hours. Before being sent to the laboratory, the collected biomaterial is stored in a sterile container placed in a special box or refrigerator at a certain temperature. On the container for collecting urine indicate the time of the first and last emptying of the bladder, the patient's personal data, date of birth.

for catecholamines

In the laboratory, the biomaterial is examined for several indicators that depend on the age and gender of the individual. The unit of measurement of hormones is mcg / day, each type has its own norms:

Adrenalin. Valid values for citizens over 15 years old are 0-20 units.
Norepinephrine. The norm for the age category from 10 years old is 15-80.
Dopamine. The indicator corresponds to the normal values of 65-400 at the age of 4 years.

The results of the study of catecholamines in urine are influenced by various factors. And since pathology in the form of a chromaffin tumor is quite rare, the indicators are often false positive. In order to reliably diagnose the disease, additional types of examinations are prescribed. If an elevated content of catecholamines is detected in patients with an already established diagnosis, this fact indicates a relapse of the disease and the ineffectiveness of the therapy. It should be remembered that taking certain groups of drugs, stress, drinking alcohol, coffee and tea affects the final result of the research. Pathologies in which an increased concentration of catecholamines is detected:

liver disease;
hyperthyroidism;
myocardial infarction;
angina;
bronchial asthma;
peptic ulcer of the duodenum or stomach;
head injury;
prolonged depression;
arterial hypertension.

A low level of hormonal substances in urine indicates diseases:

kidneys;
leukemia;
various psychoses;
underdevelopment of the adrenal glands.

Preparing for a blood test for catecholamines

14 days before the test, it is necessary to exclude drugs containing sympathomimetics (as agreed with the attending doctor). For two days, exclude from the diet: beer, coffee, tea, cheese, bananas. Quit smoking for a day. Refrain from eating for 12 hours.

Blood is taken through a catheter, which is installed a day before biomaterial sampling due to the fact that vein puncture also increases the concentration of catecholamines in the blood.

Panel "Blood catecholamines" and serotonin + urinalysis for HVA, VMK, 5-OIUK

Using such a panel, the content of catecholamines is determined: serotonin, dopamine, norepinephrine, adrenaline and their metabolites. The indications for this study are as follows:

determination of the causes of hypertensive crises and arterial hypertension;
for the purpose of diagnosing neoplasms of the nervous tissue and adrenal glands.

More information can be obtained when prescribing a daily urine test to determine the level of catecholamines due to the fact that their synthesis during this period is influenced by:

pain;
cold;
stress;
trauma;
heat;
physical stress;
asphyxia;
any kind of loads;
bleeding;
the use of drugs of a narcotic nature;
decrease in blood glucose levels.

With diagnosed arterial hypertension, the concentration of catecholamines in the blood approaches the highest bar of normal values, and in some cases increases by about two times. In a stressful situation, adrenaline in the blood plasma increases tenfold. Due to the fact that catecholamines in the blood are quickly neutralized, it is appropriate to detect them in urine for the diagnosis of pathological conditions. Practitioners prescribe tests for the concentration of norepinephrine and adrenaline mainly to diagnose hypertension and pheochromocytoma. In young children, in order to confirm neuroblastoma, it is important to determine the metabolites of norepinephrine and epinephrine, as well as dopamine.

In order to obtain reliable information about catecholamines in the analysis of urine, the presence of their decay products is also determined: HVA (homovanilic acid), HVA (vanillylmandelic acid), normetanephrine, metanephrine. The excretion of metabolic products normally exceeds the excretion of a complex of hormonal substances. The concentration of metanephrine and VMK in urine is greatly overestimated in pheofromocytoma, which is important for making a diagnosis.

It is a breakdown product of adrenaline and noradrenaline, it is found in the daily analysis for catecholamines. Indications for the appointment of the analysis are neuroblastoma, tumors and evaluation of the work of the adrenal glands, hypertension and crises. The study of this metabolite allows us to draw a conclusion about the synthesis of adrenaline and norepinephrine, and also assists in the diagnosis of neoplasms and the evaluation of the adrenal medulla.

Serotonin

In oncological practice, for the detection of argentaffinoma, a special type of tumor, such an indicator in the blood as catecholamine serotonin is important. It is considered one of and is a highly active biogenic amine. The substance has a vasoconstrictive effect, takes part in the regulation of temperature, respiration, pressure, kidney filtration, stimulates the smooth muscles of the intestines, blood vessels, bronchioles. Serotonin can cause platelet aggregation. Its content in the body is detected using the metabolite 5-OIUA (hydroxyindoacetic acid) of urine. The content of serotonin is increased in cases of:

carcinoid tumor of the abdominal cavity with metastases;
hypertensive crises in the diagnosis of pheochromocytoma;
neuroendocrine tumors of the prostate, ovaries, intestines, bronchi;
pheochromocytoma;
metastasis or incomplete removal of a neoplasm after surgery.

In the body, serotonin is converted to hydroxyindoleacetic acid and excreted in the urine. The concentration of this substance in the blood is determined by the amount of excreted metabolite.

Catecholamines - what is it? These are useful substances for any individual, necessary for an instant response of the body to an irritant: stress or fear. A blood test shows the presence of hormones immediately at the time of taking the biomaterial, and a urine test - only for the previous day.