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Lecture
HORMONES.
MOLECULAR TRANSMISSION MECHANISMS
HORMONAL SIGNAL

Lecture plan
Hormones. Hormone-like substances
Biochemistry of intercellular communications, cellular receptors
membranes and their role in cellular regulation and integration
metabolism. Molecular mechanisms transduction
hormonal signal. Apoptosis.
Molecular mechanisms of action of protein-peptide hormones
cytosolic mechanism of action of steroids and
thyroid hormones.

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SYSTEMS OF INTERCELLANEOUS INT

1. Central and peripheral nervous systems
through electrical impulses and neurotransmitters;

2. The endocrine exerts a distant action by means of

signaling molecules or hormones of the endocrine glan

3. Paracrine and autocrine systems through

 hormone-like substances of local action: prostaglandins,
Gastrointestinal hormones, histamine;
4. Immune system through specific proteins : cytokine
antibodies

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HORMONES
is a highly active, specialized chemical
compounds ;
- humoral factors of distant action ;
- synthesized in the body specialized
glands of internal secretion ;
- are released directly into the blood ;
- provide interconnection (integration) betwee
separate bodies ;
- are regulators of metabolism

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Hormone CLASSIFICATION
by chemical nature and mechanism of action
1. Amino acid and protein peptide
hormones are the extracellular membrane
mechanism of action :
 adrenaline, glucagon, tropical hormones
pituitary, vasopressin, oxytocin, parathormone,
calcitonin and others.

2. Hormones of lipid nature - cytosolic

intracellular mechanism of action:
thyroid, sexual, hormonal forms of vitamins D 3

and A, corticosteroids

Stages of the membrane mechanism of action of h

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amino acid and protein nature

hormone (adrenaline) is the primary messenger
BLOOD

target cell receptors: ionotropic

metabotropic
tyrosine kinase

G-protein transducers
cell membrane
intracellular enzymes:
adenylate cyclase, guanylate cyclase,
phospholipase C

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cAMP, cGMP, Ca +2 / KM
secondary messengers, ITF (inositol triphosphate)
secondary intermediariesDAG (diacylglycerol)
 or "messengers " "Small molecules":
reactive NO, 2CO,
oxygen species,SN.

enzymes- A, C, G
protein kinases
phosphorylated executive, or
effector protein enzymes

biological effects of hormone action:

change in metabolic rate

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MEMBRANE RECEPTORS
these are complex proteins of glycopro
structural areas (domains):
• a) extracellular (recognizable) on the surfac
plasma membranes;
• b) transmembrane - provides spatial
receptor orientation;
• c) intracellular - binds the receptor
with a hormonal signal transmission system,
namely with G-protein - transducer;

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 CHARACTERISTICS OF RECEPTORS
• Ionotropic - combine the functions of the receptor an
ion channel. Activated by ions, hormones,
by neurotransmitters. Joining them opens the ionic
channel and causes ion currents. Signal Transmission -
the fastest - in seconds.
• Metabotropic - typical for the action of protein horm
complexes with G-protein contribute to the formation of
messengers. Signal transmission - in minutes.
• Tyrosine kinase - perform functions simultaneously
receptor, transducer and enzyme. These are receptors
insulin

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G- Proteins are transducers

Types:
1 . Activators of adenylate cyclase and synthesis
cAMP (adrenaline, glucagon, parathormone);
2. Adenylate cyclase inhibitors and activators
phosphodiesterases. Reduce cAMP
(somatostatin, prostaglandins, angiotensin III
3. Activators of phospholipase C (vasopressin);
4. GTP activators (oncoprotein families).
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SECONDARY MESSANGERS
these are substances , signaling molecul
a) are synthesized in the target cell unde
exposure to protein hormones, or increa
( Ca +2 ) their concentration;
b) and activate a chain of enzymes that
carry out specific, final
biochemical reactions in the cell;

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REPRESENTATIVES OF SECONDARY MESSAN

1.Cyclic adenosine monophosphate cAMP:

- Synthesized by adenylate cyclase with ATP;

- The signal is transmitted through G-protein;
- The main function is the activation of hormon
enzymes - phosphoprotein kinase A ;
- Phosphoprotein kinase A activates executive
enzymes;
- through cAMP realize their effects adrenaline,
glucagon, tropical pituitary hormones, etc.

2. Cyclic guanosine monophosphate cGM

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- It is synthesized by guanylate cy
with GTP ;
- The signal is transmitted without the part
- Activates protein kinases G , which
phosphorylate transporting proteins
chlorine ions, relaxing smooth muscles
vessels and hearts;
- Through cGMP implement their effects:
Na-urethral hormone; intestinal toxins
bacteria, etc.

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3. Calcium calmodulin (Ca +2 / KM)
- structure: protein - calmodulin + 4 Ca +2 ions ;
- Function: intracellular activation
protein kinase C enzymes ,
- protein kinases C phosphorylate executive
calcium-dependent enzymes: phosphodiestera
phosphorylase, protein kinase, phospholipase A
 - through
hormones Ca +2: calcitonin,
/ KM realize their effects
parathormone,
neurotransmitters
- regulates biological processes: muscle contracti
microtubules, cell motility, activity
lipolytic enzymes

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4. Inositol triphosphate (ITP or IF3)
5. Diacylglycerol (DAG)
ITP activates phospholipase C, which stim
Ca +2 release into the cytosol and activation
protein kinases;
DAG shows activity through
protein kinase C , regulates activity
growth factors, cell proliferation.
Through them, hormones exert their effects
vasopressin, oxytocin, angiotensin and othe

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6. "SMALL" MOLECULES : reactive oxygen sp

 free radicals, "mediators"
signals, ofof
initiators the intercellular
apoptosis.
• Oh2- (COP) superoxide radical:
vasoconstrictor (narrows blood vessels), regulate
AT2 into cells;

• H 2AT
2 - hydrogen peroxide: modifies proteins,

by Cis and Met oxidation;

• OCl - - hypochlorite ion: oxidant of thio- and ami
proteins and enzymes, a regulator of their activit
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7 SMALL MOLECULES: Nitrogen Monoxide

signaling molecule, free radical
.
It is synthesized by AK arginine under the action of NO syn
EFFECTS
- CNS mediator: lowers heart rate, promotes relaxation (expansion)
vessels - vasodilator , blood flow to the myocardium, processes
inflammation.
- Activates enzymes: adenylate and guanylate cyclase,
prostaglandinsynthetase.
- It inhibits enzymes: cytochrome oxidase, catalase.

Drugs: nitroglycerin, viagra, etc. manifest themselves

action through NO, which is due to the formation of
relaxes the muscles of the vessels .

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8. SMALL MOLECULES: Carbon Monoxide

 A signaling molecule, a volatile gas transmitter.
It flows freely through cell membranes, no
called ' undertake receptors and directly
interacts with enzymes inside the cell .
• Synthesized during heme catabolism under action
heme oxygenase enzyme.
• Effects are realized through the activation of the secon
cGMP messenger , namely:
relaxes blood vessels, dilates bile ducts,
slows down intestinal motility, activates
platelets .

9. SMALL MOLECULES: Hydrogensulfide

2S) (H
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Chemically active signaling molecule,

gas transmitter.
It is synthesized by AK cysteine and homocysteine
Effects:
- vasodilator - dilates vessels;
- stimulant of processes of filtration in kidneys;
- antiplatelet - counteracts platelet aggregation;
- CNS mediator - in neurons promotes cAMP synthesis, regulates
synaptic activity of neurons and glia
Pathology:
Violation of production2 Sof
is N.
the basis of molecular
mechanisms of development of a number of pathologies:
cardiovascular disease, thrombosis,
renal failure, etc .
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CYTOSOL MECHANISM OF ACTION
hormones of lipid nature
Main stages:
1. Penetration of the hormone into the cell.
2. Connection with the cytosolic receptor.
3 . Interaction of hormone-receptor complex i
nuclei with a specific DNA region -
promoter.
4. Activation of transcription of specific genes .
5. Synthesis of proteins that realize the action of
The effect occurs and goes away within hours

Page 20 Cytosolic mechanism of action of hormones of lipid nature

Page 21

LIPID MESSANGERS. Eicosanoids

arachidonic acid derivatives: prostaglandins,
prostacyclins, thromboxanes, leukotrienes,
isoprostanes
• prostaglandins : through the smooth muscle of the ve
reduce or increase blood pressure, relax or
narrow the bronchi, stimulate the muscles of the uterus
inhibit NSI secretion, an inflammatory mediator.
• prostacyclins - vasodilators, antiplatelet agents.
• thromboxanes stimulate platelet aggregation,
mediators of inflammation.
• isoprostanes - vasoconstrictors.

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APOPTOSIS
It is a natural, evolutionarily formed,
genetically programmed death
innocuous and unnecessary cells .
In the cell there kolaps- fall
pressure in the nucleus, breaking DNA into frag
The cell dries, shrinks and divides into
apoptotic fragments that are phagocytosed.
Some diseases are a consequence of the disorde
 mechanism of apoptosis:
AIDS, neurodegenerative pathologies, ischem
lesions (increased apoptosis), cancer,
leukemia (not the ability of cells to apoptos

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A. Receptor-dependent apoptosis
Mediated, with the participation of special receptors on th
Death mediators:
• 1. Fas-ligand (Fas-L) - integral protein -
lymphocytes, including the mechanism of death.
• 2. Tumor necrosis factor (TNF) is integral
T-killer protein.
• 3. Interleukins, interferons start
cell death program that activates the cascade
caspase enzymes. Caspases are proteinases,
which destroy cellular proteins, block
DNA replication and repair contribute
of cell disintegration into apoptotic fragments.

B. RECEPTOR-INDEPENDENT APOPTOSIS
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It is induced by signaling molecules inside the cell.

Mediators:
• Reactive oxygen species - block cell proliferation.
N2AT 2 and OH - activate apoptotic caspases.
• Nitrogen monoxide NO - activates membrane bound
 a sphingomyelinase enzyme that produces signals
apoptosis of ceramide and sphingosine.
• Ceramides and sphingosine - reduce transmembrane
potential of mitochondria, destroy proteins and DNA.
• Perforins - proteins that form a channel in the membran
target cells for proapoptotic penetration
proteases - granzymes .
• Xenobiotics - substances of cytostatics .

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Apoptosis induced by Fas / Fas-L and
cytokines .
• Fas receptor and cytokine receptors (receptors
death). Attaching inductors activates them
pro-apoptotic caspase-triggering proteins
enzymes.
• Caspases (proteinases) destroy cellular proteins,
inhibit DNA replication and repair,
promote the disintegration of cells into apoptoti

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• History. Muller introduced the concept of

glands of internal secretion
 • 1840 Graves and Bazedov described the clinica
picture of thyrotoxicosis, or Bazedova
diseases.
• 1849 Berthold transplanted the testes
castrated roosters, which restored them
potency.
• 1855 Addison described the clinic for bronze
diseases (adrenal hypofunction).

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• 1878 The 80-year-old Brown Secard invented the

of youth (extract from the testis of the cock), whi
tried on myself.
• 1889–90 Mering and Minkowski installed
diabetes mellitus association with impaired func
of the pancreas.
• 1938 Feuerter discovered a diffuse endocrine
system.
• 1953–54 Sanger deciphered the structure
and synthesized it in 1957.
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Apudocytes are of nerve origin,

have endocrine and neuro-
source functions and produce as
hormones and biogenic amines (adrenalin
norepinephrine, serotonin).
Apudocytes scattered singly or
accumulations in all organs and tissues,
except skeletal muscle.

Localization of apudocytes:
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1. neurosecretory cells of the hypothalamus, brain

the pituitary gland;
2. pinealocytes of the epiphysis;
3. Brain chromaffin cells
adrenal glands;
4. C-cells of the thyroid gland;
5. insulocytes of islets of a pancreas;
6. chromatin cells of the gastrointestinal mucosa,
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At the point of synthesis

• 1 ) hormones of central endocrine formations -
hypothalamus, pituitary, epiphysis;
• 2 ) hormones of peripheral endocrine formations -
adrenal, thyroid and parathyroid
glands;
• 3) hormones of organs of mixed functions -
pancreas, thymus, reproductive glands;
• 4) hormones of the diffuse endocrine system .

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Cascade Gain System

HORMONAL SIGNAL
• When moving from one level to another, it occurs
10-fold increase in hormonal signal.
• 1 molecule of the hypothalamus releasing factor stimula
synthesis of 10 tropical pituitary hormone molecules.
• Tropical hormone stimulates the synthesis of 100 molecu
executive hormone.
 • The
the latter through
formation the receptors
of millions of the target
of molecules of thecell causes
relevant m

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By the nature of biological action

1. True or "true" hormones:
hypothalamus, pituitary, epiphysis, thyroid and
parathyroid glands, adrenal glands; islands
Pancreas langerhans, male and
female genital glands.
II. Hormone-like substances (hormones,
parahormones, tissue hormones, histogormones,
local action hormones).

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True hormones
• are remote communication signals and
fabrics;
• synthesis by specialized cells
 endocrine
• secreted glands;
into blood, lymph, cerebrospinal fluid
fluid;
• have a distant effect;
• in violation of their synthesis or transport
there are characteristic types of pathology.

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• Hormonoids are signals of communication bet

closely spaced cells,
tissues, organs;
• have neuro- or non-endocrine
origin;
• are synthesized by specialized cells
different organs and tissues;
• excreted into the intercellular fluid
• act on target cells in their place
synthesis, ie characterized by local
(isocrine) action

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Types of isocrine action:

• 1. Autocrine regulation - free soluble action
 forms of regulatory molecules on membrane receptor
the cells that produce them.
That's how growth factors work.

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• 2 . Paracrine regulation is the action of free solu

forms of synthesizing regulatory molecules
effector cells, to receptors adjacent
"Target cells":
growth factors, necrosis, cytokines, acetylcholine

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 3. Juxtacrine
• - interaction regulation
of membrane-bound form
regulator (eg cytokine) effector
cell with a membrane receptor adjacent
cells are the target.

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4. Retrocrine action
• the action of free cytokine receptors that are deta
from the effector cell to the membrane bound
forms of cytokines remotely located cells -
targets.
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Examples of hormone-like substances

• Gastrin - stomach, 12 duodenum

Stimulation of pepsin and NSI secretion
• Cholecystokinin - 12-hollow and small intestine
Stimulation of pancreatic secretion and contractions
gallbladder
• Secretin - 12-pelvic and small intestine
Secretion of bicarbonates
• Motilin - the small intestine
Stimulates intestinal motility
• Somatostatin - pancreas
It inhibits insulin synthesis

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• 2. Biogenic amines : adrenaline, norepinephrine

dopamine, serotonin, melatonin, histamine.
• 3. Eicosanoids - arachidonic acid derivatives:
prostaglandins, thromboxanes, prostacyclins,
leukotrienes.
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• 4. Hormones of the immune system : thymosin,

thymopoietin, thymosterin - stimulants
lymphopoiesis and mediators of the immune sy
cytokines, insulin-like growth factor (IGF).
• 5. Brain opioid peptides - endorphins and
enkephalins - have morphine-like
effect.

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• 6. Natriuretic peptides (NUPs) are stimulatin

urinary excretion of Na + , Cl– and water,
increase urine output.
• 7. Kinin - angiotensin peptides
blood systems . Kinins reduce blood pressure;
angiotensins - increase blood pressure
 • 8regulator
. Calcitriol is an active
of calcium form of vitamin D 3 -
metabolism.

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• 9. Cytomedins (intermedin ):
• a) - n eptydni growth factors - regulate
cell proliferation and differentiation;
• b) cytokines or interleukins - growth factors,
leukocyte secreted and formed
cellular and immune responses.

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Regulation of hormone secreti

• Nervous or neurohumoral - through influenc
nervous system.
 • For example, response syndrome
on stressors (Selye) is accompanied
by activating the synthesis of the hormones of
the pituitary gland - the adrenal gland

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• Metabolic regulation through impact

of blood metabolites at chemoreceptors. So,
hyperglycemia stimulates insulin synthesis and
inhibits adrenaline.
• Tropical regulation (humoral) through influenc
tropical pituitary hormones for secretion
hormones of peripheral endocrine glands
on the principle of "forward-reverse"
communication or "plus-minus" interactions.

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 • pituitary
•
TSH thyroid hormones
•
• Thyroid
• gland

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Types of communication between cells:

• Direct cell contact - across cells

channels are distributed by ions and signal
molecules.
• Cell contact with the involvement of signaling m
(bioregulators) local action:
• a) neurotransmitters,
B) histohormones
• Cell contact with bioregulators
distant action (true hormones )
 Mechanisms of action of hormon
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• The mechanism and speed of signal transmissio

There are 3 types of alarms:
• The first type for neurotransmitters. Effect
arises and quenches in a millisecond. Mediator,
joining the ionotropic receptor,
opens channels for ions, calls
membrane reloading and function change
"Target cells".

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• The second type (membrane) - for protein-

peptide hormones, catecholamines,
prostaglandins. The effect occurs and disappea
minutes through interaction with metabotrop
receptors on the plasma membrane, and in
in the middle of the cell through the intracellul
transduction and amplification system
hormonal signal:
Page 51

• Metabotropic type receptors -

joining the ligand activates
transducer G-protein, and through it
membrane enzymes.
Secondary messengers are formed, which,
activating protein kinases or inhibiting
protein phosphatase phosphorylate
executive proteins.

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Sphingosine and ceramides

• Formed from membrane sphingolipids under

the effects of activated sphingomyelinases
cytokines, growth factors, FAS ligands.
Ceramides and sphingosine-1-P activate
protein kinases that regulate cell proliferation
 and apoptosis.

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apoptosis:

• Reactive oxygen species and nitric oxide.

• Ceramides, sphingosine.
• Perforins - proteins that form a channel in
target cell membranes where they penetrate
granzymes are pro-apoptotic proteases.
• Xenobiotics (cytostatics) .

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Apoptosis induced by active forms

oxygen and nitrogen

• These factors activate the membrane bound

initiating sphingomyelininase
apoptosis (ceramides and sphingosine).
 • Direct and direct action of hydrogen peroxide an
of a hydroxyl radical on apoptotic caspases.

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The hormones of the hypothala

• Liberins, or releasing hormones (release -

dismiss)
• Statins
• Oligopeptides of 3-5 amp.
• Regulation of secretion : nervous, metabolic.
The mechanism of action of the membrane.

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• 1. Somatoliberin - an STG stimulant.

• 2. Corticoliberin - corticotropin (ACTH);
•• 3.
4. Tyroliberin - thyrotropin
Gonadoliberin - follitropin(TSH);
FSH and lutropin
LH.
• 5. Prolactoliberin - prolactin;
• 6. Melanoliberin - melanotropin (MSG).
• 1. Somatostatin inhibits STG synthesis;
• 2.Prolactostatin - prolactin;
• 3. Melanostatin - MSG.

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Adenohypophysis hormones

• 1. Growth hormone group : somatotropin, prolactin.

2. The group of tropical hormones (glycoproteins):
TSG, TSG, (FSH, LH).
• 3. Group of derivatives of POMC (proopiomelanocortin) : A
LTG, MSG, endorphins.
Synthesis of endocrinocytes of adenohypophysis and place
Secretion regulation : nervous, metabolic, by principle
direct-feedback.

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 Growth hormone
somatotropic (somatotropin,
hormone) protein STH-
• Regulates postnatal body growth.
• Stimulates protein biosynthesis;
• causes hyperglycemia (inhibits glucose transport in
cells stimulating gluconeogenesis);
• activates lipolysis and the release of fatty acids into the
• has lactogenic properties.
• The biological action of STH is realized through somato
(insulin-like growth factors).
• Active STG is excreted at the onset of sleep.

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Pathology of STH secretion

• STH hypofunction from childhood leads to

pituitary nanism or dwarfism .
(receptor blockade on target cells)
STH hyperfunction from childhood leads to
giantism , and in adults to acromegaly
(disproportionate development of skeletal bone
internal organs). The reason is a tumor
the pituitary gland.
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60
61
62
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• Prolactin (lactotropin, mamotropin,

luteotropic hormone) is a polypeptide.
Stimulates breast development, lactation.
Excessive synthesis of prolactin causes
amenorrhea and galactorrhea

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Tropical hormones of the adenoh

• Thyrotropin (TSH) - stimulates synthesis
of iodothyronines in the thyroid gland.
Stimulates secretion of tyroliberin, inhibit -
iodothyronines.
Pathology - central thyrotoxicosis.
• Gonadotropins (TSG) - development and funct
sex glands and production of sex hormones.
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• Follitropin (FSH) - the maturation of follicles in

ovaries and spermatogenic proliferation
epithelium and Sertoli cells in the testes.
• Lutropin (LH). In women it stimulates ovulatio
and the formation of a yellow body during pre
yellow body development and production
progesterone.
• In men, it stimulates testosterone synthesis in
cells of Leydig.

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POMC products
• Corticotropin (ACTH). Peptide. Activates synthe
glucocorticoids and partly androgens and
mineralocorticoids in the cortex of the adrenal g
melanocyte-stimulating effect.
• Lipotropins (LTG) - stimulate lipolysis
Page 68

Hormones of the middle lobe of the pitui

• The pituitary intermediate is only active in

the embryonic period and the later stages
pregnancy producing melanoma-tropin (MSG
• MSG stimulate melanocyte activity
skin through tyrosinase converting
tyrosine in melanins.

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(neurohypophysis)

Cyclic nonapeptides. Synthesis in the hypothalam

Neurophysin transports protein.
 • Vasopressin (ADH antidiuretic hormone).
• There are 2 types of receptors for vasopressin:
• V1 - on hepatocyte membranes, smooth
muscle vessels, platelets.
V2 - tubule cells and loops of Henle kidneys.

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The effects of ADH

• Extra-renal function - reduces vascular muscles
increases blood pressure, stimulates glycogeno
platelet aggregation
• renal - reduces urine output. Through
hyaluronidase depolymerizes hyaluronic
acid and increases the permeability of the tubu
water kidney (reabsorption).
• When synthesis is reduced, diabetes mellitus.

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Oxytocin
 • Mechanism of action of membrane, through cG
Activates smooth muscle contraction
uterus, stimulates labor and lactation after
childbirth.

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Practical use of pituitary hormones

• Corticotropin - for adrenal hypofunction

• Somatotropin - for pituitary dwarfism
• By reducing the function of the sex glands in men and wo
in infertility - analogues of follitropin - serum and
menopausal gonadotropins.
• To stimulate lactation after childbirth - lactin
Page 73

Intermedin or melanotropin - for treatment

degenerative changes of the retina.
• Adiurecrine contains vasopressin and
used in diabetes mellitus.
• Oxytocin and its analogues - for stimulation
childbirth activities.

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Epiphysis hormones are "third eye", biological
body clock - derivatives of Three

Serotonin is synthesized in the light of day.

Regulates vascular smooth muscle, GI,
bronchial tubes;
causes inflammatory and allergic reactions,
activates blood coagulation processes;
Page 75

• Melatonin (synthesis at night). Synchronizer

circadian rhythms, sleep regulator.
• inhibits the secretion of THG (delayed sexual in
development and function of the glands),
• controls the pigmentation of the skin of lower
Has hypoglycemic, hypocholesterolemic,
antioxidant and antitumor action -
inhibition of hormone synthesis decreases
life expectancy and vice versa

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Thyroid hormones.
• A. Thyrocyte hormones - thyroid (iodothyronine
iodinated tyrosine derivatives (diode-, triiod-,
tetraiodothyronine (T 4 or thyroxine).
Page 77

• Mechanism of action through plasma and cytosolic

receptors.
• 1) Increase basic exchange by enhancing
oxygen uptake and tissue separation
respiration and oxidative phosphorylation, inhibit
∆μH + generation and ATP synthesis.
• 2) Stimulate catabolism of proteins, fats,
carbohydrates (increase the content of glucose, fat
acids and amino acids in the blood);
• 3) Stimulate morphogenesis - body growth, developm
brain differentiation;
• 4) activate cardiovascular activity;

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• Hypofunction of the thyroid gland since childho
cretinism (mental and physical
underdevelopment).
• In adults, hypothyroidism - myxedema (mucous
edema) - slowing down catabolism of proteins
carbohydrates (obesity, hypoglycemia), worsen
 memory, drowsiness, apathy, edema. It is treat
thyroid hormones.

Page 79

• Endemic goiter - compensatory

enlargement of the thyroid gland at
iodine deficiency in water and food (more com
mountain areas).
• Treat iodine preparations for
prevention of iodized salt.

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Mixedema
Page 82

• Hyperfunction - thyrotoxicosis or Bazedov

disease - increased secretion of pituitary TSH.
Increased catabolism of proteins, fats, carbohydr
(weight loss, negative nitrogen balance,
hyperglycemia), fever
(separation of oxidative phosphorylation and
tissue respiration), tachycardia, exophthalmos,
enlargement of the gland.

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 • Treated with iodothyronine antagonists
(mercazolyl, potassium perchlorate),
radioactive isotopes of iodine (I 131 ),
promptly.

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84

hormones

• Use thyroidin (T3 and T4) and

synthetic triiodothyronine at different
forms of hypothyroidism (cretinism,
myxedema), with obesity with manifestations
hypothyroidism, cerebral pituitary
diseases that flow from
hypothyroidism, with endemic goiter.
Page 86

B. Neuroendocrine cells hormones .

• Calcitonin (peptide) . Secretion regulation: through
increasing the concentration of Ca and P in the blood
• Biological role - prevention of hypercalcemia
(hypocalcaemia, hypophosphatemia). It stimulates
deposition of calcium and phosphorus salts into tissues
bones and teeth, inhibits their resorption.
• The hormone level increases during pregnancy and lact
baby to protect mother's body from Ca loss

Page 87

(parathyrin) is a protein
Mechanism of action - membrane, through cAMP and calcium calm
Role: - regulator of calcium and phosphorus homeostasis, causes
hypercalcemia, but hypophosphatemia
• Activates osteoblasts that produce in bone tissue
activator of osteoclasts, which causes calcium and phosphate to es
blood.
• In the intestine stimulates the absorption of calcium through the fo
calciotriol and synthesis of calcium-binding proteins.
• Increases calcium reabsorption in the kidneys but inhibits phospha
Page 88

• Hypofunction - spasmophilia (skeletal cramps

muscle because of its low calcium concentration
blood). It is treated by the introduction of CaCl 2 s
• Hyperfunction - osteoporosis (calcium absorption
phosphorus from bones and teeth), bone fracture
teeth.
• Excess calcium in the blood leads to
calcification of internal organs and muscles,
formation of urinary stones.

Page 89

The practical use of hormone regulators

phosphorus-calcium metabolism

Parathyroid - for hypoparathyroidism for

tetany prevention.
Calcitonin preparations (calcitrin, myacalcic)
 -also
with osteoporosis,
with with(retarded
bone injuries fibrotic dysplasia, and
fracture fusion).

Page 90
Hormones of the adrenal medulla

• Catecholamines (biogenic amines): dopamin

norepinephrine, adrenaline . Synthesis of tyr
Inactivation by MAO disinfection, or
methylation
• The mechanism of action is adenylate cyclase

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• The mechanism of action is adenylate cyclase.

• Biological effects:
• 1. Reduction of vascular smooth muscle and
 increase in blood pressure, increase in frequen
heart rate, reduction of smooth
muscles of other organs;
• 2) Hyperglycemia (due to the breakdown of gly
• 3) Stimulation of lipolysis;

Page 92

Use of catecholamines.

• To stimulate heart rate and

increase in blood pressure.
• for allergic reactions, anaphylactic shock;
• for the removal of bronchospasm;
• in case of insufficiency of peripheral circulation,
as a local vasoconstrictor.

Page 93

Adrenal cortex hormones

 (corticosteroids)

1. glucocorticoids - cortisol, cortisone,

corticosterone
2. mineralocorticoids - aldosterone, 11-
deoxycorticosterone, 18-oxycorticosterone
3. Sex hormones.
The mechanism of action of cytosolic

Page 95
94

Cholesterol synthesis .
Activates ACTH synthesis, corticoliberin, state
stress, anxiety, fear (Selye theory -
adaptation syndrome).
Aldosterone synthesis regulates renin-angio-
tensile system, K +, Na + , ACTH.
Metabolized hormones in the liver, kidneys,
the gut. Excreted as 17-COP,
sulfates, glucuronates.
Page 96

The role of glucocorticoids

• Hyperglycemic action:
1. activation of synthesis of enzymes of gluconeoge
2. release of amk from glucose synthesis proteins
3. inhibition of glucose in tissues
• Fat-mobilizing action (activation of lipolysis) thr
stimulation of secretion of adrenaline and STG.
• Stimulation of erythropoiesis and hemoglobin syn
through activation of erythropoietin expression

Page 97

• Immunosuppressive and antiallergic action t

blocking lymphocyte proliferation.
• Anti-inflammatory effect - inhibition of activit
phospholipase A2, which releases arachidonic
phospholipid acid for inflammatory synthesis
eicosanoids.
• Increase the body's resistance to stress
Page 98
Addison or bronze disease
(hypofunction or hypocorticism)
When glucocorticoid deficiency is reduced
resistance of the body to stress, infectious,
chemical factors; there is hypoglycemia,
weight loss.

Aldosterone Deficiency Disrupts Water-

mineral exchange. The body loses sodium and
water but retains potassium: occurs
hyperpolarization of membranes leading to
hypotension, muscle weakness

At patients the pigmentation of skin and

mucous membranes as a consequence of compensatory
increased ACTH secretion

Page 99
100

Hypercorticism - Itsenko-Cushing's disease

• Cause - adrenal tumors, pituitary gland.

• Decreases glucose tolerance and occurs
hyperglycemia and other symptoms of steroid diabetes.
• A dramatic increase in protein catabolism causes
thinning of the skin, reduction of muscle mass and
negative nitrogen balance.
• A characteristic manifestation is osteoporosis.

Page 102
101

Practical use of corticosteroids .

• Synthetic glucocorticoids (prednisone,
dexamethasone, etc.) are more active than natural horm

• Used in allergies and autoimmunity

diseases (rheumatism, rheumatoid arthritis,
collagenoses, bronchial asthma, neurodermatitis) as
immunosuppressive, anti-inflammatory, desensitizing.

• Of mineralocorticoid analogues used

deoxycorticosterone in Addison's disease,
myasthenia gravis, a common muscle weakness.

• The immunosuppressive action of glucocorticoids allows

use them in transplantation of organs and tissues
to suppress the rejection reaction.

Page 103

Sex hormones are sex hormones

• A. Ovarian hormones - female hormones: estrogens
(passion train), estran derivatives, or C 18 steroids) and
progestogens (derivative derivatives, C 21 -steroids).
• Cytosolic mechanism of action. Control of secretion throu
and LH. Cholesterol synthesis is excreted in the form
 sulfates and glucuronides
• Estrogens (estradiol, estrone and estriol) - in the 1st half
menstrual cycle
• Progesterone is synthesized in the 2nd half by the yellow
and during pregnancy by the placenta.

Page 105
104

The effects of estrogens:

• 1. stimulation of growth and maturation of reproductive
provision of reproduction, formation of secondary
sexual characteristics (development of mammary gland
skeleton by female type, development of laryngeal cartil
• 2. regulation of changes in the mucous membrane of the
menstrual cycle time (progesterone);
• 3. delay of calcium and phosphorus salts in the bones - at
estrogen deficiency - osteoporosis;

Page 106

• Have antioxidant effect and increase

women's resistance to vascular disease -
 increase the synthesis of HDL and reduce - LPN
• In ovarian hypofunction in women - manifesta
masculinization (beard, mustache, rough voice
• Progesterone deficiency produces up to
disorders of sexual cycles and miscarriages.
• Estrogen hyperproduction - a risk factor
tumors of the uterus and mammary glands.

Page 107

estrogens.
• Use hormones and synthetic drugs
(diethylstilbestrol and sinestrol) in violation
sexual cycles, to preserve pregnancy.
• Synthetic analogues of estrogens that inhibit synthesis an
secretion of gonadotropic hormones, but have no other
properties of estrogens, use as
contraceptives.
• Synthetic compounds with anti-estrogenic activity
compete with estradiol for receptors. Example,
tamoxifen - for the treatment of breast cancer.

Page 108
 Testes (testes) hormones are androgens

• Synthesized in Leydig cells and partially in

adrenal cortex and ovaries in women with
cholesterol (C19-steroids). Inactivated before
17-COP. Secretion is regulated by FSH and LH.
The maximum production is 7-9 in the morning
• Cytosolic mechanism of action .

Page 110
109

The biological role of androgens:

• 1. sexual differentiation;
• 2. spermatogenesis;
• 3. formation of secondary sexual characteristic
• 4. Anabolic action: stimulation of protein synth
muscles and increasing their weight.
• 5. formation of psychophysical status
husband
Page 111

• Hypogonadism (testosterone deficiency), or

eunuchidism. Before puberty
impaired development of secondary sexual
and then regression.
• Hypogonadism - underdevelopment of the sexual
organs and secondary sexual characteristics, atro
musculature, obesity, disorders
psychophysiological reactions.

Page 113
112

• Testosterone and its synthetic preparations

analogues are used for hypofunction of the testes
and functional disorders of the reproductive syst
in men.
• Synthetic (retabolil, nerabol, phenobolin)
have anabolic action and minimal sex
activity and used for fractures,
in conditions accompanied by exhaustion and
 negative nitrogen balance

Page 114

Pancreatic hormones
• The endocrine part is represented by islands
Langerhans-Sobolev:
α-cells secrete glucagon,
β-cells (70% of the islets) are insulin,
δ-cells - somatostatin

Page 115

Insulin
• from lat. insula is an island.
• This is the first hormone in which and
protein nature, and which
was obtained synthetically.
• Insulin was discovered in 1902 by L. Sobolev, isol
F.Banting and Best in 1921. Amino acid
the sequence was deciphered by F. Senger (1955)

Page 116

• Insulin is a simple protein. M.M. 5700. Contains 5

amino acid and is made of 2 chains,
interconnected by 2 disulfide
bridges. Circuit A contains 21 amps, and B - 30:

Page 117

• Human, pig and bull insulins are similar. So,

Human and pig insulins are different
amino acid. Therefore, pork insulin has
 less antigenic activity
for replacement and is used
therapy.
• Use human insulin for this purpose,
which is obtained through genetic engineering.

Page 118

Synthesis of insulin

Secretion regulation - metabolic through

increase of glucose level.

Page 119

• Insulin binds to plasma

 tyrosine kinase receptors
• It manifests itself through the synthesis of second
intermediaries (Ca2 + ions, cyclic nucleotides,
ITF, DAG).

Page 120

Biological action of insulin

• The only hormone that causes hypoglycemia :
• 1. stimulates glucose transport into muscle cells,
adipose tissue, liver, phosphorylating
glucose transporter-4.
• 2. accelerates glucose utilization through activation
glycolysis, pentose pathway, glycogen synthesis,
stimulating the activity of key enzymes .
Page 121

• 3. inhibits glycogenesis and gluconeogenesis

• 4. Has a lipogenic effect: stimulates synthesis
fatty acids from glucose and fats, inhibits
lipolysis .
• 5. stimulates anabolic processes, accelerates
transport of amino acids into cells and synthesis
proteins.
• 6. Has a growth-stimulating effect

Page 122

• Is a consequence of insulin deficiency.

• Diabetes:
Type I (insulin dependent),
Type II (non-insulin dependent).
• In type I diabetes, insulin synthesis and secretion are imp
• Type II diabetes is caused by a decrease in sensitivity
tissue to insulin, caused by a decrease in the amount
membrane receptors.
• In all cases of diabetes, catabolic processes
predominate over anabolic
Page 123

Glucagon
• Peptide of 29 amino acids.
• Secretion is regulated by blood glucose levels.
• Membrane action mechanism through cAMP
• Insulin antagonist. The main target
liver hepatocytes and adipocytes.
• Increases glucose and fatty acids levels
blood, stimulating glycogenolysis and lipolysis.

Page 124

Thymus hormones
• The thymus is required for formation and activity
the body's immune system.
• Contains hormones of peptide nature:
• 1.Tymosin stimulates immunocompetence
T-lymphocytes and their proliferation;
• 2. Thymopoietins I and II - differentiation
thymocytes;
• 3. Thymic humoral factor activates reactions
T cells for antigens,

Page 125

• Normal immunological status

broken or nonexistent.
• There may be no thymus at birth
(both cellular and humoral immunity are abse
or insufficient development of the thymus in ch
or the synthesis of humoral antibodies is impai
with normal cellular immunity
(agammaglobulinemia) or no cellular
immunity during normal antibody synthesis
(Di George's syndrome).