The integration of cells, tissues and organs into a single human organism, its adaptation to various changes in the external environment or the needs of the organism itself is carried out due to nervous and humoral regulation. The system of neurohumoral regulation is a single, closely related mechanism. The connection between the nervous and humoral regulatory systems is clearly visible in the following examples.
First, the nature of bioelectric processes is physicochemical, i.e. consists in the transmembrane movements of ions. Secondly, the transfer of excitation from one nerve cell to another or an executive organ occurs through a mediator. And finally, the closest connection between these mechanisms is traced at the level of the hypothalamic-pituitary system. Humoral regulation in phylogenesis appeared earlier. Later, in the process of evolution, it was supplemented by a highly specialized nervous system. The nervous system exercises its regulatory influences on organs and tissues with the help of nerve conductors that transmit nerve impulses.
It takes a fraction of a second to transmit a nerve signal. Therefore, the nervous system triggers rapid adaptive reactions when the external or internal environment changes. Humoral regulation is the regulation of vital processes with the help of substances entering the internal environment of the body (blood, lymph, liquor). Humoral regulation provides longer adaptive responses. Factors of humoral regulation include hormones, electrolytes, mediators, kinins, prostaglandins, various metabolites, etc.
The highest form of humoral regulation is hormonal. The term “hormone” was first used in 1902 by Starling and Bayliss in relation to the substance they discovered, produced in the duodenum, secretin. The term “hormone” in Greek means “stimulating action”, although not all hormones have a stimulating effect.
Hormones are biologically highly active substances synthesized and released into the internal environment of the body by endocrine glands, or endocrine glands, and have a regulatory effect on the functions of organs and body systems remote from the place of their secretion. The endocrine gland is an anatomical formation devoid of excretory ducts, the only or main function of which is the internal secretion of hormones. The endocrine glands include the pituitary gland, pineal gland, thyroid gland, adrenal glands (medulla and cortex), parathyroid glands.
Unlike internal secretion, external secretion is carried out by exocrine glands through the excretory ducts into the external environment. In some organs, both types of secretion are simultaneously present. The endocrine function is carried out by the endocrine tissue, i.e. an accumulation of cells with an endocrine function in an organ that has functions not related to the production of hormones. The organs with a mixed type of secretion include the pancreas and gonads. One and the same endocrine gland can produce hormones that are unequal in their action. For example, the thyroid gland produces thyroxine and thyrocalcitonin. At the same time, the production of the same hormones can be carried out by different endocrine glands. For example, sex hormones are produced by both the sex glands and the adrenal glands.
The production of biologically active substances is a function not only of the endocrine glands, but also of other traditionally non-endocrine organs: kidneys, gastrointestinal tract, heart. Not all substances formed by specific cells of these organs satisfy the classical criteria for the concept of “hormones”. Therefore, along with the term “hormone”, the concepts of hormone-like and biologically active substances (BAS), local hormones have also been used recently. So, for example, some of them are synthesized so close to their target organs that they can reach them by diffusion without entering the bloodstream. The cells that produce such substances are called paracrine cells. The difficulty of accurately defining the term “hormone” is especially evident in the example of catecholamines – adrenaline and norepinephrine. When considering their production in the adrenal medulla, they are usually called hormones, when it comes to their formation and secretion by sympathetic endings, they are called mediators.
Regulatory hypothalamic hormones – a group of neuropeptides, including the recently discovered enkephalins and endorphins, act not only as hormones, but also perform a kind of mediator function. Some of the regulatory hypothalamic peptides are found not only in the neurons of the brain, but also in special cells of other organs, for example, the intestine: this substance P, neurotensin, somatostatin, cholecystokinin, etc. The cells that produce these peptides, according to modern concepts, form a diffuse neuroendocrine system, consisting of cells scattered in different organs and tissues.
The cells of this system are characterized by a high content of amines, the ability to capture amine precursors, and the presence of amine decarboxylase. Hence the name of the system based on the first letters of the English words Amine Precursors Uptake and Decarboxylating system – APUD system – a system for capturing amine precursors and decarboxylating them. Therefore, it is legitimate to talk not only about the endocrine glands, but also about the endocrine system, which unites all the glands, tissues and cells of the body, secreting specific regulatory substances into the internal environment.
The chemical nature of hormones and biologically active substances is different. The duration of its biological action depends on the complexity of the structure of the hormone, for example, from fractions of a second for mediators and peptides to hours and days for steroid hormones and iodothyronines. Analysis of the chemical structure and physicochemical properties of hormones helps to understand the mechanisms of their action, to develop methods for their determination in biological fluids and to carry out their synthesis.
Classification of hormones and BAB by chemical structure: Derivatives of amino acids: derivatives of tyrosine: thyroxine, triiodothyronine, dopamine, adrenaline, norepinephrine; tryptophan derivatives: melatonin, serotonin; histidine derivatives: histamine. Protein-peptide hormones: polypeptides: glucagon, corticotropin, melanotropin, vaso-pressin, oxytocin, peptide hormones of the stomach and intestines; simple proteins (proteins): insulin, somatotropin, prolactin, parathyroid hormone, calcitonin; complex proteins (glycoproteins): thyrotropin, follitropin, lutropin. Steroid hormones: corticosteroids (aldosterone, cortisol, corticosterone); sex hormones: androgens (testosterone), estrogens and progesterone. Derivatives of fatty acids: arachidonic acid and its derivatives: prostaglandins, prostacyclins, thromboxanes, leukotrienes.
Despite the fact
that hormones have different chemical structures, they share some common biological properties.
General properties of hormones: Strict specificity (tropism) of physiological action. High biological activity: hormones exert their physiological effect in extremely small doses. Distant nature of action: target cells are usually located far from the site of hormone formation. Many hormones (steroids and amino acid derivatives) are not species specific. Generalized action. Prolonged action.
Four main types of physiological action on the body have been established: kinetic, or starting, causing a certain activity of the executive organs; metabolic (metabolic changes); morphogenetic (differentiation of tissues and organs, effect on growth, stimulation of the morphogenetic process); corrective (change in the intensity of the functions of organs and tissues).
The hormonal effect is mediated by the following main stages: synthesis and entry into the bloodstream, forms of transport, cellular mechanisms of hormone action. From the place of secretion, hormones are delivered to target organs by circulating fluids: blood, lymph. In the blood, hormones circulate in several forms: 1) in a free state; 2) in combination with specific proteins of blood plasma; 3) in the form of a non-specific complex with plasma proteins; 4) in an adsorbed state on blood cells. At rest, 80% falls on the complex with specific proteins. Biological activity is determined by the content of free forms of hormones. The bound forms of hormones are like a depot, a physiological reserve, from which hormones pass into an active free form as needed.
A prerequisite for the manifestation of the effects of the hormone is its interaction with receptors. Hormonal receptors are special proteins of the cell, which are characterized by: 1) high affinity for the hormone; 2) high selectivity; 3) limited binding capacity; 4) the specificity of localization of receptors in tissues. Dozens of different types of receptors can be located on the same cell membrane. The number of functionally active receptors can vary under various conditions and in pathology. So, for example, during pregnancy, M-cholinergic receptors disappear in the myometrium, and the number of oxytocin receptors increases. In some forms of diabetes mellitus, there is a functional insufficiency of the insular apparatus, i.e. the level of insulin in the blood is high, but some of the insulin receptors are occupied by autoantibodies to these receptors. In 50% of cases, receptors are localized on the membranes of the target cell; 50% – inside the cage.
Mechanisms of hormone action. There are two main mechanisms of action of hormones at the cell level: the implementation of the effect from the outer surface of the cell membrane and the implementation of the effect after the penetration of the hormone into the cell.
In the first case, the receptors are located on the cell membrane. As a result of the interaction of the hormone with the receptor, a membrane enzyme, adenylate cyclase, is activated. This enzyme promotes the formation from adenosine triphosphoric acid (ATP) of the most important intracellular mediator for the implementation of hormonal effects – cyclic 3,
5-adenosine monophosphate (cAMP). cAMP activates the cellular enzyme protein kinase, which implements the action of the hormone. It has been established that hormone-dependent adenylate cyclase is a common enzyme, which is acted upon by various hormones, while hormone receptors are multiple and specific for each hormone. In addition to cAMP, secondary mediators can be cyclic 3,5-guanosine monophosphate (cGMP), calcium ions, inositol triphosphate. This is how peptide, protein hormones, tyrosine derivatives – catecholamines act. A characteristic feature of the action of these hormones is the relative speed of the onset of the response, which is due to the activation of previously synthesized enzymes and other proteins.
In the second case, receptors for the hormone are located in the cytoplasm of the cell. Hormones of this mechanism of action, due to their lipophilicity, easily penetrate through the membrane into the target cell and bind in its cytoplasm with specific receptor proteins. The hormone-receptor complex is included in the cell nucleus. In the nucleus, the complex disintegrates, and the hormone interacts with certain areas of nuclear DNA, resulting in the formation of a special messenger RNA. Messenger RNA leaves the nucleus and promotes the synthesis of a protein or protein enzyme on the ribosomes. This is how steroid hormones and tyrosine derivatives – thyroid hormones – act. Their action is characterized by a deep and long-term restructuring of cellular metabolism.
Inactivation of hormones occurs in the effector organs, mainly in the liver, where hormones undergo various chemical changes by binding to glucuronic or sulfuric acid, or as a result of the action of enzymes. Partially hormones are excreted in the urine unchanged. The action of some hormones can be blocked due to the secretion of hormones that have an antagonistic effect.
Hormones perform the following important functions in the body: Regulation of growth, development and differentiation of tissues and organs, which determines physical, sexual and mental development. Ensuring the adaptation of the body to changing conditions of existence. Ensuring the maintenance of homeostasis.
Functional classification of hormones: Effector hormones are hormones that act directly on the target organ. Triple hormones are hormones whose main function is to regulate the synthesis and release of effector hormones. Excreted by the adenohypophysis. Releasing hormones are hormones that regulate the synthesis and release of hormones of the adenohypophysis, mainly triple ones. They are secreted by the nerve cells of the hypothalamus.
Types of hormone interactions. Each hormone does not work alone. Therefore, it is necessary to consider the possible results of their interaction.
Synergy is the unidirectional action of two or more hormones. For example, adrenaline and glucagon activate the breakdown of liver glycogen to glucose and cause an increase in blood sugar.
Antagonism is always relative. For example, insulin and adrenaline have opposite effects on blood glucose levels. Insulin causes hypoglycemia, adrenaline causes hyperglycemia. The biological significance of these effects comes down to one thing – improving the carbohydrate nutrition of tissues.
The permissive action of hormones is that the hormone itself, without causing a physiological effect, creates conditions for the response of a cell or organ to the action of another hormone. For example, glucocorticoids, without affecting vascular muscle tone and liver glycogen breakdown, create conditions in which even small concentrations of adrenaline increase blood pressure and cause hyperglycemia as a result of glycogenolysis in the liver.
The regulation of the activity of the endocrine glands is carried out by nervous and humoral factors. The neuroendocrine zones of the hypothalamus, pineal gland, adrenal medulla and other parts of the chromaffin tissue are regulated directly by nervous mechanisms. In most cases, the nerve fibers that go to the endocrine glands regulate not the secretory cells, but the tone of the blood vessels, on which the blood supply and the functional activity of the glands depend. The main role in the physiological mechanisms of regulation is played by neurohormonal and hormonal mechanisms, as well as direct effects on the endocrine glands of those substances whose concentration is regulated by this hormone.
The regulatory effect of the central nervous system on the activity of the endocrine glands is carried out through the hypothalamus. The hypothalamus receives signals from the external and internal environment through the afferent pathways of the brain. The neurosecretory cells of the hypothalamus transform afferent nerve stimuli into humoral factors, producing releasing hormones. Releasing hormones selectively regulate the functions of adenohypophysis cells. Among the releasing hormones, liberins are distinguished – stimulants of the synthesis and release of hormones of the adenohypophysis, and statins – secretion inhibitors. They are called the corresponding tropic hormones: thyreoliberin, corticoliberin, somatoliberin, etc. In turn, the tropic hormones of the adenohypophysis regulate the activity of a number of other peripheral endocrine glands (adrenal cortex, thyroid gland, gonads). These are the so-called direct downstream regulatory communications.
In addition to them, there are reverse ascending self-regulating links within these systems. Feedback can come from both the peripheral gland and the pituitary gland. By the direction of the physiological action, feedbacks can be negative and positive. Negative links are self-limiting system operation. Positive connections start her up. So, low concentrations of thyroxine through the blood increase the production of thyroid-stimulating hormone by the pituitary gland and thyroliberin – by the hypothalamus. The hypothalamus is significantly more sensitive than the pituitary gland to hormonal signals from the peripheral endocrine glands. Thanks to the feedback mechanism, a balance is established in the synthesis of hormones, which responds to a decrease or increase in the concentration of hormones of the endocrine glands.
Some endocrine glands, such as the pancreas, parathyroid glands, are not influenced by pituitary hormones. The activity of these glands depends on the concentration of those substances, the level of which is regulated by these hormones. Thus, the level of parathyroid hormone and thyroid calcitonin is determined by the concentration of calcium ions in the blood. Glucose regulates the production of insulin and glucagon by the pancreas. In addition, the functioning of these glands is carried out due to the influence of the level of antagonist hormones.