Peptide hormones (small peptides, oligopeptides, simple proteins, glycoproteins) – the most numerous and diverse in composition and variable in a comparatively biological terms, the class of hormonal compounds.
Among the peptide hormones containing 3 to 200 amino acid residues are all the hypothalamic hormones and pituitary hormones, as well as insulin and glucagon secreted by the pancreas.
According to the peculiarities of the chemical structure, properties and physiological functions of the hormones entering into it, this class can be divided into families:
1) neurohypophysisal peptides;
2) hypothalamic peptide releasing factors;
4) oligopeptidnyh pituitary hormones of some ACTH;
5) oligopeptidnyh hormones such as glucagon and hormones of the gastrointestinal tract;
7) polypeptide hormones regulating the exchange of calcium, and polypeptide hormones regulating the exchange of phosphorus;
8) single-chain (monomeric) peptide hormones of some STG;
9) dimeric glycoprotein hormones.
It is assumed that representatives of each of the majority of the families listed have emerged at the earliest stages of the evolution of vertebrates from the common hormonal progenitor through a series of consecutive mutations and duplications of the coding gene, as well as the associations of modified genes into larger ones.
This assumption does not apply to the family of parathyroid hormone and calcitonin. The typology of hormones in this case is based not on the evolutionary-structural principle, but on the orientation of their physiological effects.
Peptide hormones also include erythropoietin, thymus hormones, somatomedins, some neurosecretory hormones of insects, etc.
An analysis of the functional properties of various sections of the peptide chain of neurohypophysis hormones showed that the ring part of the hormone molecule, and especially the amino acid in the 3-position, is responsible for binding them to the receptors of the corresponding target organs.
Obviously, the presence of the 3-position Fen provides the best binding of peptides mainly vasopressin receptors cells excretory organs and arterioles. Presence in the same position of isoleucine causes the greatest affinity of the hormone to oxytocin receptors of myometrium cells (smooth muscle of the uterus) and myoepithelial mammary gland formations. However, both types of ring part can still bind, albeit with varying degrees of intensity, to both types of receptors and compete with each other for binding. Apparently, the structure of the entire 1-6-loop of neurohypophysial peptides is responsible for the principle possibility of hormone-receptor interaction, and the residues in the 3rd position of the loop determine the strength of this interaction with one or another type of receptors and the specificity of the effect. The role of the acton, according to existing concepts, the side chain and the tyrosine residue are in the 2-position.
At present, the main directions of the development of studies of protein – peptide hormones are:
1) study of the fine structural and functional organization of genes and mRNA encoding protein mammalian protein hormones, identification of the main regulatory elements of these genes, analysis of their structure and mechanisms of tissue-specific multiorgonal (multifactorial) regulation.
2) the study of genes and mRNA encoding factors of protein nature that regulate the expression of these proteinaceous peptide hormones in mammals, analyze their structure and mechanisms of interaction with regulatory regions of the promoter regions of protein and peptide hormone genes;
3) study of the structural and functional organization of the protein – peptide hormones themselves, revealing the functional significance of individual amino acid domains, elucidating the regular relationships between the amino acid sequence and the functional activity;
4) elucidation of the molecular mechanisms of the action of protein-peptide hormones in the target cell, decoding the chain of molecular signals realizing the effect of the peptide hormone from the surface of the cell membrane receptor on the gene located in the chromosome.
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Through what active compounds of cell hormones realize their effect?
The highest form of humoral regulation is hormonal. The term “hormone” was first applied in 1902 by Starling and Beiliss in relation to the substance discovered by them, produced in the duodenum, secretin. The term “hormone” in Greek means “stimulating to action,” although not all hormones have a stimulating effect.
Hormones are biologically highly active substances that are synthesized and released into the internal environment of the body by the endocrine glands or glands of internal secretion, and which have a regulatory effect on the functions of the 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 primary function of which is the internal secretion of hormones. Endocrine glands include the pituitary gland, epiphysis, thyroid gland, adrenal glands (cerebral and cortical substance), parathyroid glands.
Unlike internal secretion, external secretion is carried out by exocrine glands through the excretory ducts to the external environment. In some organs, both types of secretion are present simultaneously. The endocrine function is realized by the endocrine tissue, i.e. accumulation of cells with an incretory function in an organ possessing functions not related to the production of hormones. To organs with a mixed type of secretion are the pancreas and the sex glands. The same gland of internal secretion can produce hormones that are not the same 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 the sex glands and adrenal glands.
The production of biologically active substances is a function not only of endocrine glands, but also of other traditionally non-endocrine organs: the kidneys, the gastrointestinal tract, the 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” recently used the concepts of hormone-like and biologically active substances (BAA), hormones of local action. For example, some of them are synthesized so close to their target organs that they can reach them by diffusion without getting into the bloodstream. Cells that produce such substances are called paracrine. The difficulty of precise definition of the term “hormone” is especially well seen in the example of catecholamines – adrenaline and norepinephrine.
Regulatory hypothalamic hormones – a group of neuropeptides, including newly discovered enkephalins and endorphins, act not only as hormones, but also perform a peculiar mediator function. Some of the regulatory hypothalamic peptides are found not only in neurons of the brain, but also in specific cells of other organs, for example, the intestine: substance P, neurotensin, somatostatin, cholecystokinin, etc. Cells that produce these peptides form a diffuse neuroendocrine system, consisting of cells scattered across 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 by the first letters of the English words Amine Precursors Uptake and Decarboxylating system – APUD-system – the system for trapping amine precursors and their decarboxylation. 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, which release specific regulatory substances into the internal environment.
The chemical nature of hormones and biologically active substances is different. The complexity of the structure of the hormone depends on the duration of its biological effect, for example, from fractions of a second in mediators and peptides to hours and days in steroid hormones and iodothyronines. Analysis of the chemical structure and physico-chemical 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: tyrosine derivatives: thyroxine, triiodothyronine, dopamine, epinephrine, noradrenaline; derivatives of tryptophan: melatonin, serotonin; histidine derivatives: histamine.
Steroid hormones: corticosteroids (aldosterone, cortisol, corticosterone); sex hormones: androgens (testosterone), estrogens and progesterone.
Derivatives of fatty acids: arachidonic acid and its derivatives: prostaglandins, prostacyclin, thromboxanes, leukotrienes.
Despite the fact that hormones have different chemical structure, they are characterized by some common biological properties.
Common properties of hormones:
1. Strict specificity (tropism) of physiological action.
2. High biological activity: hormones exert their physiological effect in extremely small doses.
3. Distant nature of the action: target cells are usually located far from the place of formation of the hormone.
4. Many hormones (steroid and derivatives of amino acids) do not have specific specificity.
5. Generalized action.
6. Prolonged action.
There are four main types of physiological action on the body: kinetic, or trigger, causing certain activities of the executive bodies; metabolic (metabolic changes); morphogenetic (differentiation of tissues and organs, effect on growth, stimulation of the formative process); Correcting (changes in the intensity of the functions of organs and tissues).
The hormonal effect is mediated by the following main stages: the synthesis and intake into the blood, the forms of transport, the cellular mechanisms of the action of hormones. From the place of secretion, hormones are delivered to the 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 the blood plasma; 3) in the form of a nonspecific complex with plasma proteins; 4) in the adsorbed state on the shaped elements of the blood. In a state of rest, 80% is in the complex with specific proteins. Biological activity is determined by the content of free forms of hormones. Associated forms of hormones are, as it were, a depot, a physiological reserve, from which hormones pass into an active free form as needed.
An obligatory condition for the manifestation of the effects of the hormone is its interaction with the receptors. Hormonal receptors are specific cell proteins, which are characterized by: 1) high affinity for the hormone; 2) high selectivity; 3) bound binding capacity; 4) specificity of receptor localization 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 different conditions and in pathology. So, for example, in pregnancy in myometrium, M-cholinergic receptors disappear, 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 the receptors are localized on the membranes of the target cell; 50% inside the cell.
Mechanisms of action of hormones. There are two main mechanisms of action of hormones at the cell level: the realization of the effect from the outer surface of the cell membrane and the realization 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, the membrane enzyme, adenylate cyclase, is activated. This enzyme promotes the formation of an important intracellular mediator from the adenosine triphosphate acid (ATP), the realization of hormonal effects – cyclic 3,5-adenosine monophosphate (cAMP). cAMP activates the cellular enzyme protein kinase, which realizes the action of the hormone. It has been established that hormone-dependent adenylate cyclase is a common enzyme on which various hormones act, while hormone receptors are multiple and specific for each hormone. Secondary mediators other than cAMP may be cyclic 3,5-guanosine monophosphate (cGMP), calcium ions, inositol triphosphate. So the peptide, protein hormones, tyrosine derivatives – catecholamines.
In the second case, the receptors for the hormone are in the cytoplasm of the cell. Hormones of this mechanism of action, by virtue of their lipophilicity, easily penetrate the membrane inside the target cell and bind in its cytoplasm with specific receptor proteins. The hormone-receptor complex enters the cell nucleus. In the nucleus, the complex decays, and the hormone interacts with certain parts of the nuclear DNA, which results in the formation of a special matrix RNA. The matrix RNA leaves the nucleus and promotes synthesis on the ribosomes of protein or protein-enzyme. Thus, steroid hormones and tyrosine derivatives act as thyroid hormones. Their action is characterized by a deep and long-term reorganization of cellular metabolism.
Inactivation of hormones occurs in the effector organs, mainly in the liver, where the 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:
1. Regulation of growth, development and differentiation of tissues and organs, which determines physical, sexual and mental development.
2. Ensuring the adaptation of the organism to the changing conditions of existence.
3. Providing maintenance of homeostasis.
Functional classification of hormones:
1. Effector hormones are hormones that affect directly the target organ.
2. Triple hormones are hormones, the main function of which is the regulation of the synthesis and isolation of effector hormones. Excreted adenohypophysis.
3. Releasing hormones are hormones that regulate the synthesis and secretion of adenohypophysis hormones, mostly triple ones. Isolated by the nerve cells of the hypothalamus.
Types of interaction of hormones. Each hormone does not work alone. Therefore, it is necessary to take into account the possible results of their interaction.
Synergism is a 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 levels.
Antagonism is always relative. For example, insulin and epinephrine have the opposite effect on the level of glucose in the blood. Insulin causes hypoglycemia, adrenaline – hyperglycemia. Biological importance of these effects is reduced to one – the improvement of carbohydrate nutrition of tissues.
Permissive action of hormones is that the hormone, without causing a physiological effect, creates conditions for the response of the cell or organ to the action of another hormone. For example, glucocorticoids, without affecting the tone of vascular musculature and the decomposition of liver glycogen, create conditions in which even small concentrations of adrenaline increase blood pressure and cause hyperglycemia as a result of glycogenolysis in the liver.