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GENERAL PRINCIPLES OF
METABOLISM REGULATION.
HORMONES.
Levels of the homeostasis
regulation
Highest level –
nervous system
Intermediate hormonal
regulation
Intracellular
(enzymes)
Hormones – organic biologically active compounds
of different chemical nature that are produced
by the endocrine glands, enter directly into blood
and accomplish humoral regulation of the
metabolism of compounds and functions on the
organism level.
Hormonoids (tissue hormones) – compounds that
are produced not in glands but in different
tissues and regulate metabolic processes on the
local level, but some of them (serotonin,
acetylcholine) enters blood and regulate
processes on the organism level.
Specific stimulus for hormones
secretion is:
-nervous impulse
-concentration of the certain
compound in blood passing through
the endocrine gland
Endocrine glands:
1.
2.
3.
4.
5.
6.
7.
of
8.
9.
Hypothalamus
Pituitary
Epiphysis
Thymus
Thyroid gland
Parathyroid glands
Langergans’ islands
pancreas
Epinephrine glands
Sex glands
Classification of hormones
according to chemical nature
1.
2.
3.
4.
5.
Proteins: hormones of anterior pituitary
(except ACTH), insulin, parathyroid hormone.
Peptides: ACTH, calcitonin, glucagon,
vasopressin, oxytocin, hormones of
hypothalamus (releasing factors and statins).
Derivatives of amino acids: catecholamins
(epinephrine and norepinephrine), thyroxin,
triiodthyronin, hormones of epiphysis.
Steroid (derivatives of cholesterol):
hormones of the cortex of epinephrine
glands, sex hormones.
Derivatives of polyunsaturated fatty
(arachidonic) acids: prostaglandins.
Fate of hormones in the organism
•Are secreted directly into the blood
•Peptide and protein hormones are
secreted by exocytosis
•Steroid (lipophilic) hormones
continuously penetrate the membrane
(they are not accumulated in cells, their
concentration in blood is determined by
the speed of synthesis)
Transport of hormones in blood
Protein and peptide nature – in free state
Steroid hormones and hormones of thyroid gland –
bound with alpha-globulins or albumins
Catecholamines – in free state or bound with
albumins, sulphates or glucuronic acid
Reach the target organs
Cells have the specific receptors to certain
hormone
Receptors of hormones
Two groups:
-placed on the surface of membrane – peptide and
protein hormones, prostaglandins;
-placed inside the cells (cytoplasm, nucleus) – steroid and
thyroid hormones
Model of the insulin receptor ( Jacobs, Cautrecasas, 1982)
Inactivation of hormones
After biochemical effect hormones are released
and metabolized
Hormones are inactivated mainly in liver
Inactive metabolites are excreted mainly with
urine
Half-time life
-from several min to 20 min – for the majority of
hormones
-till 1 h – for steroid hormones
-till 1 week – for thyroid hormones
THE FINAL EFFECTS OF
HORMONES ACTION
1.
2.
3.
4.
Change the permeability of cell membrane,
accelerate the penetration of substrates, enzymes,
coenzymes into the cell and out of cell.
Acting on the allosteric centers affect the activity
of enzymes (Hormones penetrating membranes).
Affect the activity of enzymes through the
messengers (cAMP). (Hormones that can not
penetrate the membrane).
Act on the genetic apparatus of the cell (nucleus,
DNA) and promote the synthesis of enzymes
(Steroid and thyroid hormones).
It is located in the
base of forebrain
between thalamus
and pituitary gland.
Has wide anatomical
bonds and collects
information from
another structures
of brain.
Collect information
from blood flowing
through
hypothalamus.
HYPOTHALAMUS
Tight
anatomical
bonds with
pituitary
gland
Two groups of
hormones
related to
anterior and
posterior lobes
of pituitary
Hypothalamus and posterior
lobe of pituitary
3 peptides are synthesized
Migrate along axons into
posterior lobe of pituitary
1) Antidiuretic hormone
(vasopressin)
2) Oxytocin
3) Neurophysin (promotes
transport of vasopressin
and oxytocin into pituitary
gland)
Hypothalamus and anterior pituitary
Bound with
anterior pituitary
by the capillary net
– hypothalamic
portal system
Releasing factors
and statins rich
the anterior
pituitary via this
system
Secretion of liberins and statins by hypothalamus is
carried out under the effect of nervous impulses and as
result of the change of concentrations of certain
hormones in blood (feedback regulation).
Releasing factors (liberins) stimulate secretion of
pituitary hormones; statins - inhibit.
•somatoliberin,
•thyroliberin,
•corticoliberin,
•foliliberin,
•prolactoliberin,
•luteinising-hormone liberin,
•melanoliberin
•somatostatin,
•prolactostatin,
•melanostatin
HYPOPHISIS - “conductor of the
hormonal orchestra of the organism”
There are hormones
of anterior,
posterior and
intermediate lobes
of pituitary gland.
The most important
– anterior lobe
(secrets tropic
hormones)
Tropic – because
stimulate functions
of peripheral
endocrine glands
TROPIC HORMONES OF PITUITARY
Somatotropic hormone (growth hormone)
Chemical nature – simple protein
It is secreted continuously during the whole life
Secretion is stimulated
inhibited by somatostatin
by
somatoliberin,
is
Main function – stimulates somatic growth
of organs and tissues, particularly bones,
cartilages, muscles.
Acts both directly and through the stimulation of the
formation of polypeptides somatomedins (insulin-like
growth factors).
ILGF are synthesized in liver
The effect of STH on the protein
metabolism



Promotes the entrance of AA into cells,
Inhibits catabolism of proteins and AA
Activates the synthesis of proteins, DNA, RNA.
The effect of STH on the carbohydrate
metabolism



Antiinsulin hormone – activates insulinase of liver
Activates the exit of glucose from liver
Inhibits the conversion of glucose into fat
The effect of STH on lipid
metabolism


Stimulates the decomposition of lipids (lipolisis)
Stimulates the oxidation of fatty acids.
In the inherited
hypoplasia of pituatary
gland dwarfism is
developed.
For the treatment GH is
used.
Hyperproduction of GH
before puberty and
before the completion of
ossification results in
gigantism
Yao Defen, the
tallest women
in the life,
2.36 м
Hyperfunction of pituitary inadults
results in acromegaly –
unproportionally intensive growth
of particular body parts (fingers,
nose, lower jaw, tongue, inner
organs).
Cause –
tumor of
anterior
pituitary
Adrenocorticotropic hormone (АCTH)
Chemical nature – polipeptide
Secretion is stimulated by corticoliberin
Feedback regulation of the speed of secretion
depending on the cortisol level
Controls the cortex of epinephrine gland where
cortisol is produced:
-promotes the increase of cholesterol content in
epinephrine glands cortex and its conversion into
corticosteroids;
-activates the passing of glucose into epinephrine
glands and pentose phosphate cycle (NADPH
synthesis)
-has melanocyte stimulating activity
Cushing’s disease
Cushing's disease – hyperproduction of
ACTH (adenoma in a pituitary gland) which
in turn elevates cortisol.
Obesity, particularly of the trunk and face
(“moon face“) with sparing of the limbs;
striae (stretches of the skin)
Proximal muscle weakness
Hirsutism (facial male-pattern hair growth)
Insomnia,
impotence,
amenorrhoea,
infertility
Heart diseases, hypertension
Polyuria,
hypokalemia
hyperglycemia,
glucosuria (steroid diabetes)
Kidney bones
Depression, anxiety
Hyperpigmentation
Thyrotropic hormone (ТТH)
Chemical structure – protein (glycoprotein)
Secretion is stimulated by thyroliberin
The speed of secretion is regulated according to
the feedback regulation by thyroid hormones
It is necessary for the normal functioning of
thyroid gland:
-promotes the accumulation of iodine in thyroid
gland and its insertion into tyrosine;
-stimulates the synthesis of try- and
tetraiodthyronin
Gonadotropic hormones
Follicle-stimulating гормон
Chemical nature – protein (glycoprotein)
Secretion is stimulated by foliliberin
Function: stimulates the function of follicles in
women and spermatogenesis in men
Luteinizing hormone
Chemical nature – protein (glycoprotein)
Secretion is stimulated by luliberin
Function: stimulates the follicular growth and
conversion of the follicle into a corpus luteum in
women and secretion of testosterone in men
Prolactin
Chemical nature – protein
Secretion is stimulated by prolactoliberin
Functions:
-stimulates the function of mammary glands
(lactation);
-provides the body with sexual gratification
after sexual acts
-stimulates the function of corpus luteum
(progesterone secretion);
-stimulates the growth of tissue of prostatic
gland in men;
-responsible for the mother instinct
Lipotropic hormones
Chemical nature – simple proteins
Functions:
-mobilization of lipids from depot;
-melanocyte stimulating function;
-decrease Ca in blood
THE INTERMEDIATE LOBE OF
PITUITARY
Melanocyte stimulating hormone (melanotropin)
Chemical nature – peptide
Functions:
-stimulates melaninogenesis;
-adaptation of vision in darkness
POSTERIOR LOBE OF PITUITARY
Vasopressin (antidiuretic hormone)
Chemical nature – peptide
Functions:
-activates hyaluronidase which decomposes
hyaluronic acid in the membranes of kidney
canaliculi – increases the reabsorption of water
in kidneys;
-contractions arterioles and capillaries –
increases blood pressure
Insufficiency – diabetes insipidus (polyuria, low
density of urine, dehydratation)
Oxytocin
Chemical nature – peptide
Functions:
-stimulates the contraction
of smooth muscles (of
uterus during labor)
-stimulates milk secretion
(contraction
of
muscle
fibers around mammary
alveoli)
Using:
-for labor stimulation;
-to
stop
after
labor
hemorrhage;
-for stimulation of milk
secretion
EPIPHYSIS (PINEAL GLAND)
Produces:
 Мelatonin from serotonin (regulates the
pigment metabolism)
 Adrenoglomerulotropin – stimulates
secretion of
mineralocorticoids in
the epinephrine
glands cortex.
 Inhibitor of
gonadotropin –
inhibits the synthesis
of prolactin,
cholesterol
PANCREAS
Exocrine and endocrine parts
Endocrine – Langerhans islets (alpha-,
beta- and delta-cells)
Alpha-cells: glucagon
Beta-cells: insulin
Delta-cells: somatostatin
Epithelium of ducts: lipocain
Insulin



Nature – protein (51 АA)
Is formed from proinsulin by proteolisis
Contains zinc

-
Regulation of the synthesis:
Glucose concentration in blood
Other hormones (somatostatin)
Sympathetic and parasympathetic nervous system
It is destroyed by insulinase (enzyme of liver)
Target cells:
 Hepatocytes
 Myocytes
 Adipocytes
In the unsufficiency – diabetes mellitus
The effect on carbohydrate metabolism
•Increases the permeability of membranes
for glucose
•Activates glucokinase (hexokinase) in
glycolysis
•Activates TAC (citrate synthase)
•Activates PPC (G-6-PDH)
•Activates glycogen synthase
•Activates pyruvate- and alpha-кetoglutarate
dehydrogenase
•Inhibits gluconeogenesis
•Inhibits the decomposition of glycogen
(glucose-6-phosphatase)
Effect on the protein metabolism
•Increases the permeability of membranes for
AA
•Activates synthesis of proteins and nucleic acids
•Inhibits gluconeogenesis
Effect on the lipid metabolism
•Activates of the lipids synthesis
•Promotes the saving of fats activating the
decomposition of carbohydrates
•Inhibits gluconeogenesis
Effect on the mineral metabolism
•Activates Na/K-АТP-аse
Glucagon
Nature – polypeptide
 Antagonist of insulin
 Synthesis is activated in fasting

Functions
 Activates
the
decomposition of
glycogen in liver
 Activates
gluconeogenesis
 Inhibits glycolysis
 Activates lipolysis
Somatostatin
 Nature
– peptide
Functions:
• Inhibits secretion of insulin and
glucagon
• Inhibits secretion of STH and TTH
• Inhibits secretion of local hormones of
intestine
Lipocain
•
•
•
Functions:
Activates the synthesis
of phospholipids in liver
Stimulates the action of
lipotropic factors
Activates the oxidation
of fatty acids in liver