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Endocrine glands (from the Greek endon - inside, crio - secrete) or endocrine
glands are specialized organs or groups of cells, the main function of which is to
produce and release specific biologically active substances into the internal
environment of the body
...
Their
cells are intertwined with an abundant network of blood and lymphatic vessels,
and waste products are released directly into the blood, lymph, and tissue fluid
...

The products produced by the endocrine glands are called hormones (Greek
hormao - excite, activate)
...
Bernard, and the term “hormone” by the English
physiologists W
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Starling in 1902
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Hormones are
formed in glandular endocrine cells, after which they enter the internal
environment, mainly into the blood and lymph
...

High biological activity
...
Thus, the concentration of the female sex hormone (estradiol) in
the blood ranges from 0
...
6 mcg (10-6 g) per 100 ml of plasma
...
The pituitary gland reacts to picograms (10-12 g) of
hypothalamic hormones, angiotensin-P, a product of endocrine cells of the
kidneys, causes a feeling of thirst in femtograms (10-15 g)
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Specificity
...
In this regard, the deficiency of any
hormone cannot be compensated for by other hormones or biologically active
substances
...
Hormones, as a rule, are transported in the blood far from the
site of formation, affecting distant organs and tissues
...

Chemical structure of hormones and their transformation in the body
According to their chemical structure, hormones can be divided into 4 main
groups:
proteins and peptides;
amino acid derivatives;
steroids;
prostaglandins
...
Some of them (follitropin,
thyrotropin, lutropin) are complex proteins, others (insulin, calcitonin, etc
...
Glucagon, vasopressin, oxytocin, and hypothalamic hormones
have a peptide structure
...
Steroid
hormones are based on the cyclic hydrocarbon core
cyclopentaneperhydrophenanthrene
...

The main stages of hormone formation and transformation can be represented as
follows:
hormone biosynthesis;
secretion, i
...
isolation from an endocrine cell;
transport by blood to peripheral tissues;
recognition of a hormonal signal by target cells;
transduction (translation) of a hormonal signal into a biological response;
suppression of the hormonal signal
...

Organs and tissues
Cells
Hormones
1
...


Thymus
Thymocytes
Thymosin, thymopoietin
3
...

Heart
Atrial myocytes
Atriopeptide, somatostatin, angiotensin-P
Organs, tissues and cells with endocrine function
No
...


Hypothalamus
Nerve cells of punctate structures
Hypothalamic neurohormones:
Posterior hypothalamus
Nerve cells of the magnocellular nuclei of the anterior hypothalamus
a) liberins: corticoliberin, thyroliberin, luliberin, folliberin, somatoliberin,
prolactoliberin, melanoliberin;
b) statins: prolactostatin, melanostatin, somatostatin
Vasopressin, oxytocin
2
...

Adrenal glands Cortex
Brain matter
Zona glomerulosa Zona fasciculata Zona reticularis
Chromaffin cells
Mineralocorticoids Glucocorticoids Sex steroids: androgens, estrogens
Adrenaline, norepinephrinelin
4
...

Parathyroid glands
Chief cells K cells
Parathyrin Calcitonin
6
...


Pancreas
Islets of Langerhans:
os-cells P-cells A-cells
Glucagon
Insulin
Somatostatin
8
...
Consequently, it depends on the structure and
expression of the genes encoding the synthesis of these hormones, as well as on
the enzymes that regulate hormone synthesis and post-translational processes
...
An
example is dwarfism due to a genetic defect in growth hormone
...
Secretion of hormones
...
The hormone packaged in vesicles or granules is
transported towards the cytoplasmic membrane
...
After this,
their lysis occurs and the hormone leaves the cell
...

Hormone secretion is an act accompanied by energy expenditure, so it is always
associated with shifts in the ATP-cAMP system
...
Therefore, a decrease in the content of
calcium ions in the extracellular environment and its entry into the endocrine cell
inevitably leads to a decrease in the secretory activity of this cell
...
Transport of hormones
...
Most hormones
form complex compounds in the blood with plasma proteins
...

Complexation with proteins is a reversible process
...

The formation of a bound form of hormones is of great physiological importance
...
Secondly, the bound form of the
hormone is its physiological reserve
...
e
...
Finally, complexation
with proteins prevents the filtration of small-molecule hormones through the
glomeruli and thereby inhibits these important regulatory processes
...
Recognition of a hormonal signal
...
During the peripheral action of hormones, various transformations occur
...
Thus,
the thyroid hormone thyroxine can be converted in tissues into triiodothyronine,
a more active hormone of the same gland
...

Transduction of a hormonal signal into a biological response is organically related
to the mechanism of action of this hormone
...
This phenomenon is called hormone reception,
and the cellular components that interact with the hormone are called receptors
...

The structure of the receptor molecule is characterized by asymmetry
...
e
...

Receptors are located either intracellularly or on the surface of the cytoplasmic
membrane
...
It is also believed that the function of recognizing
a specific hormonal signal in all cells for all hormones is carried out by a
membrane receptor, and after binding of a hormone to its corresponding
receptor, the further role of the hormone-receptor complex for peptide and
steroid hormones is different In peptide, protein hormones and catecholamines,
the hormone-receptor complex leads to the activation of membrane enzymes and
the formation of various secondary messengers (messengers) of the hormonal
regulatory effect, which realize their action in the cytoplasm, organelles and cell
nucleus
...

4
...
The adenylate cyclase - cAMP system
...
Activation of
adenylate cyclase occurs under the influence of a hormone-receptor complex, the
formation of which leads to the binding of guanyl nucleotide (GTP) to a special
regulatory stimulating protein (GS protein), after which the GS protein causes the
addition of magnesium to adenylate cyclase and its activation
...
Some hormones, on the contrary, suppress
adenylate cyclase (somatostatin, angiotensin-P, etc
...
This changes the
permeability of membranes, i
...
causes metabolic and, accordingly, functional

changes typical for the hormone
...

"Guanylate cyclase - cGMP" system
...
This is how
atrial natriuretic hormone, atriopeptide, a tissue hormone of the vascular wall,
realizes its effects
...
Examples include stimulation of cardiac
contractions under the influence of cAMP and inhibition of them by cGMP,
stimulation of contractions of intestinal smooth muscles by cGMP and inhibition
of cAMP
...
3 Phospholipase C - isositol triphosphate system
...
Iositol triphosphate causes the release of
ionized calcium from intracellular stores
...
Diacylglycerol also activates and
completes the process of phosphorylation of other proteins, while simultaneously
implementing the second pathway of hormonal effect: through the formation of
arachidonic acid, which is a source of substances with powerful metabolic and
physiological effects - prostaglandins and leukotrienes
...

4
...
The calcium-calmodulin system
...
In the cytoplasm of non-muscle cells, calcium binds to
a special protein - calmodulin, and in muscle cells the role of calmodulin is played
by troponin C
...
A short-term increase in the amount of
calcium in the cell and its binding to calmodulin is a stimulus for numerous
physiological processes - muscle contraction, secretion of hormones and release
of mediators, DNA synthesis, changes in cell motility, enzyme activity, transport of

substances through membranes
...
In the
cytoplasm there is a special cytoplasmic receptor protein with which the hormone
binds
...
All these phenomena require the long-term presence of the hormonereceptor complex in the nucleus
...
These are effects such as increased pmembrane permeability, increased
transport of glucose and amino acids, release of lysosomal enzymes, shifts in
mitochondrial energy and, in addition, an increase in cAMP and ionized calcium
...

Peptide hormones also have the ability to selectively influence gene transcription
in the cell nucleus
...

The phenomenon of internalization of hormone-receptor complexes and thereby
reducing the number of hormone receptors on the cell membrane allows us to
understand the mechanism of decreased effector sensitivity with an excess
amount of hormonal molecules, or the phenomenon of effector desensitization
...

The opposite phenomenon - sensitization, or increased sensitivity to hormones,
can be caused by an increase in the number of free receptor sites on the
membrane, both due to a decrease in internalization and as a result of the
“floating up” of active receptor binding sites
...

5
...
There are 5 types
of effects of hormones on target tissues: metabolic, morphogenetic, kinetic,
corrective, reactogenic
...
Metabolic shifts caused by hormones underlie changes in cell,
tissue, and organ function
...

Examples include the influence of somatotropin on the growth of the body and
internal organs, the influence of sex hormones on the development of secondary
sexual characteristics
...
For
example, oxytocin causes contraction of the uterine muscles, adrenaline triggers
the breakdown of glycogen in the liver and the release of glucose into the blood,
vysopressin activates the mechanism for the reabsorption of water in the
collecting ducts of the nephrons
...
Examples of the
corrective effect of hormones are the effect of adrenaline on heart rate,
activation of oxidative processes by thyroxine, and a decrease in the reabsorption
of potassium ions in the kidneys under the influence of aldosterone
...
For example, when the
anabolic processes of protein metabolism initially predominate, glucocorticoids
cause a catabolic effect, but if protein breakdown initially predominates,
glucocorticoids stimulate their synthesis
...
For example, thyroid hormones
enhance the effects of catecholamines, calcium-regulating hormones reduce the
sensitivity of the distal nephron to the action of vasopressin
...

For example, glucocorticoids have a permissive effect in relation to
catecholamines (the presence of small amounts of cortisol is necessary for the
effects of adrenaline to occur); insulin has a permissive effect in relation to
somatotropin, etc
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Extinguishing the hormonal signal
...
There are numerous mechanisms for dampening the hormonal signal
...
Along with this, destruction (catabolism) of
part of the released hormones occurs
...

Liver enzymes inactivate hormones through deamination and methylation
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Some free and conjugated hormones enter the bile and are excreted from the
body through the intestines
...
In some cases, antibodies to hormones and other
inhibitors are formed that inhibit the biological effect
...
e
...

For example, excess insulin causes hypoglycemia, which in turn induces the
secretion of contrainsular hormones
...

Modern theory of regulatory peptides
Regulatory peptides are biologically active substances synthesized by body cells of
different origins and involved in the regulation of various functions
...
In addition, they are found outside the central
nervous system in a number of endocrine glands, as well as in other organs and
tissues
...
e
...
This allows
us to believe that the separate formation of these groups of substances is
programmed in the genome, and therefore they are independent
...
These cells are considered to be the initial form
of endocrine formations
...
It has been established that these cells are able to decarboxylate aromatic
acids, the precursors of neuroamines, which made it possible to combine them
into a single system (Pearse, 1976), called the “APUD system” (after the first
letters of the English words Amine Precursor Uptake and Decarboxylating system
- system of capture and decarboxylation amine precursors)
...

Others (substance P, neurotensin, enkephalins, somatostatin) were originally
found in nervous tissue
...

The existence of this neurodiffuse endocrine system is explained by the migration
of cells from a single source - the neural crest; they are included in the central
nervous system and in the tissues of various organs, where they transform into
central nervous system-like cells that secrete neuroamines (neurotransmitters)
and peptide hormones
...

Apudocytes are also found in the kidneys, heart, lymph nodes, bone marrow,
pineal gland, and placenta
...

For a number of peptides, the localization of containing cells and the distribution
of fibers have been established
...

Long projection systems, the fibers of which reach distant areas of the brain
...

Short projection systems: neuron bodies are often located in many areas of the
brain and have a local distribution of processes (substance P, enkephalins,
cholecystokinin, somatostatin)
...
For example, substance P, VIP,
enkephalins, cholecystokinin, somatostatin are found in the vagus, celiac and
sciatic nerves
...

The existence of neuropeptides and neurotransmitters in the same neuron has
been shown: serotonin is found in the neurons of the medulla oblongata along
with substance P, dopamine along with cholecystokinin - in the neurons of the
midbrain, acetylcholine and VIP - in the autonomic ganglia
...
Under the
influence of VIP in physiological concentrations, there is a pronounced increase in
the sensitivity of muscarinic receptors to acetylcholine in the submandibular
gland of cats, and antiserum to VIP partially blocks vasodilation caused by
stimulation of parasympathetic nerves
...

Synthesis of regulatory peptides
...
e
...
Synthesis of the precursor occurs
in ribosomes, which is confirmed by the presence of messenger RNA encoding the
peptide, and post-translational enzymatic modifications with the release of active
peptides occur in the Golgi apparatus
...

Active peptides derived from one precursor form its family
...

Pro-opiomelanocortin (POMC) family
...
Depending on the set of enzymes from POMC, the
following are formed: in the anterior lobe of the pituitary gland - mainly ACTH, (3lipotropin, P-endorphin, in the intermediate - cx-melanostimulating hormone and
P-endorphin
...
These are the enzymes cathepsin B,
trypsin, carboxypeptidase, aminopeptidase, the sites of their attack are paired
amino acid residues
...

VIP family: secretin, glucagon
...

In addition, it was found that met-enkephalin and leu-enkephalin have precursors
in the form of preproenkephalin A and preproenkephalin B, respectively
...

Mechanism of action of neuropeptides:
A characteristic feature of regulatory peptides is polyfunctionality (in terms of the
mechanism and nature of effects) and the formation of regulatory chains
(cascades)
...

1
...

Neurotransmitter (neurotransmitter) is a substance that is released from the
presynaptic terminal and acts on the next one - the postsynaptic membrane, i
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performs a transfer function
...
Thus, hypothalamic luteinizing hormone releasing hormone (LH) in the
synaptic ganglia of the frog is released upon nerve stimulation through a calciumdependent process and causes a late slow excitatory postsynaptic potential
...

A neuromodulator, unlike a neurotransmitter, does not cause an independent
physiological effect in the postsynaptic membrane, but modifies the cell’s
response to the neurotransmitter
...

Types of neuromodulation:
control of neurotransmitter release from terminals;
regulation of neurotransmitter circulation;

modification of the effect of a “classical” neurotransmitter
...
The extrasynaptic action of peptides is realized in several ways
...
Paracrine action (paracrine) - occurs in areas of intercellular contact
...

B
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Examples include somatostatin
and other hypothalamic factors released in the medial eminence from some
terminals into the portal bloodstream and controlling the secretion of pituitary
hormones
...
Endocrine action
...
This mechanism includes components
required for “classical” endocrine functions - transport proteins and target cell
receptors
...
As for reception, the existence of
separate receptors has been established for opioid peptides, vasopressin, and VIL
...
translations
and transcriptions
...

Regulatory peptides are characterized by the formation of complex chains or
cascades as a result of the fact that the metabolites formed from the main
peptide are also functionally active
...

Functions of regulatory peptides:
1
...
A number of peptides influence the formation of pain as a complex
psychophysiological state of the body, including the sensation of pain itself, as
well as emotional, volitional, motor and autonomic components
...
Thus,

substance P, somatostatin, VIP, cholecystokinin and angiotensin are found in
primary sensory neurons, and substance P is a neurotransmitter secreted by
certain classes of afferent neurons
...

2
...
Evidence has been obtained that fragments of
ACTH (ACTH 4-7 and ACTH 4-10), devoid of hormonal effects, and CCmelanostimulating hormone improve short-term memory, and vasopressin is
involved in the formation of long-term memory
...
In addition, ACTH 4-10 improves attention
...

Examples include increased food motivation under the influence of opioid
peptides and weakening under the influence of cholecystokinin, calcitonin and
corticoliberin
...

VIP has a hypnotic, hypotensive and bronchodilator effect
...
Luliberin, in addition to performing a command function
(stimulation of gonadotropes of the anterior pituitary gland), regulates sexual and
parental behavior
...
Vegetative functions
...
This is the renin-angiotensin system, all components of which are
present in the brain, opioid peptides, VIP, calcitonin, atriopeptide, which have a
strong natriuretic effect
...
Thus, intracentral administration of thyrotropin-releasing hormone
and β-endorphin causes hyperthermia, while administration of ACTH and OS-MSH
causes hypothermia
...
Stress
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Thus, in experiments with various
models, it was shown that opioid peptides limit the activation of the sympathetic
nervous system and all parts of the hypothalamic-pituitary-adrenal system,

preventing the depletion of these systems, as well as the undesirable
consequences of excess glucocorticoids (suppression of the inflammatory reaction
and the thymic-lymphatic system, the appearance ulcers of the gastrointestinal
tract, etc
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Reduced
activation of the hypothalamus limits the hypersecretion of vasopressin, which
has a damaging effect on the myocardium
...
Effect on the immune system
...
On the one
hand, the ability of many peptides to modulate immune responses has now been
sufficiently studied
...
It has been established that
vasoactive intestinal peptide (VIL) inhibits all functions of lymphocytes and their
release from the lymph nodes, which is regarded as a new form of
immunomodulation
...
Lymphocyte receptors for a number of hormones have been described
...
Thus, the regulatory
leukopeptide IL-1 is able to penetrate into the brain through areas of increased
permeability of the blood-brain barrier and stimulate the secretion of
corticotropin-releasing hormone (in the presence of prostaglandin) with
subsequent it stimulates the release of ACTH and cortisol, which inhibit the
formation of IL-1 and the immune response
...
Thus, the immunopeptide acts as a trigger, which,
by closing the feedback mechanism, prevents the excess of the immune response
...
In
particular, the ability of hypothalamic neurons to secrete IL-1 has been
demonstrated
...
Neuronal

pathways in the mediobasal hypothalamus of humans and rats containing IL-1
and IL-6, as well as pituitary cells secreting these peptides, have been described
...

On the other hand, the results of immunochemical and molecular studies have
shown that immunocompetent cells secrete many peptides and hormones
associated with endocrine and neuronal activity: lymphocytes and macrophages
synthesize ACTH; lymphocytes - growth hormone, prolactin, TSH, enkephalins;
mononuclear lymphocytes and mast cells - VIP, somatostatin; thymus cells arginine, vasopressin, oxytocin, neurophysin
...

For example, ACTH secretion by lymphocytes is inhibited by glucocorticoids and
stimulated by corticotropin-releasing hormone
...

Thus, the functions of the three main regulatory systems - nervous, endocrine and
immune - are integrated into complex regulatory circles that operate on a
feedback principle
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Blalock (Blalock, 1989), provide a sensitive mechanism through which noncognitive stimuli (foreign substances) are recognized and neuroendocrine
adaptive responses are mobilized
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Since peptide hormones constitute a multifunctional system involved in the
regulation of many functions in the body, it is likely that they are involved in the
pathogenesis of various diseases
...
Whether these
changes are primary or appear as a consequence of the development of diseases
remains to be determined
...
A hypothesis
has been proposed for the existence of opioid deficiency in patients with
schizophrenia, in particular the impossibility of the formation of γ-endorphin,
which has a neuroleptic effect
...

The study of oligopeptide hormones as a regulatory system led to the
identification of a special group of diseases caused by its pathology apudopathies
...
There are
primary apudopathies, caused by the pathology of the apudocytes themselves,
and secondary ones, which arise as a reaction of apudocytes to a disturbance in
the body's homeostasis caused by a disease, the pathogenesis of which is not
primarily associated with the pathology of the APUD system (in infectious
diseases, tumor growth, diseases of the nervous system, etc
...
Examples are the following apudoms
...
Therefore, gastrinoma is clinically manifested by the
development of ulcerogenic Zollinger Ellison syndrome
...

Vipoma is a tumor of cells that secrete vasoactive intestinal peptide
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It is manifested by the development of water
diarrhea and dehydration, as well as a disorder of electrolyte metabolism
...
Somatostatinoma usually develops as a tumor of
pancreatic D cells that secrete somatostatin
...
Diagnosed by an increase in the concentration of somatostatin in the
blood plasma
...
Thus, oligopeptides
(short peptides) of the N-terminal fragment of ACTH and MSH are used to correct
attention and memory, vasopressin is used to improve memory in traumatic and
other amnesias
...
The commercial production of surfagon (an
analogue of luliberin) has begun, intended for the correction of disorders of the
reproductive system

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