GENERAL PRINCIPLES OF

METABOLISM REGULATION.
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. Hypothalamus
2. Pituitary
3. Epiphysis
4. Thymus
5. Thyroid gland
6. Parathyroid glands
7. Langergans’ islands
of pancreas
8. Epinephrine glands
9. Sex glands
 Classification of hormones
according to chemical nature
1. Proteins: hormones of anterior pituitary
(except ACTH), insulin, parathyroid hormone.
2. Peptides: ACTH, calcitonin, glucagon,
vasopressin, oxytocin, hormones of
hypothalamus (releasing factors and statins).
3. Derivatives of amino acids: catecholamins
(epinephrine and norepinephrine), thyroxin,
triiodthyronin, hormones of epiphysis.
4. Steroid (derivatives of cholesterol):
hormones of the cortex of epinephrine
glands, sex hormones.
5. 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. Change the permeability of cell membrane,
accelerate the penetration of substrates, enzymes,
coenzymes into the cell and out of cell.
2. Acting on the allosteric centers affect the activity
of enzymes (Hormones penetrating membranes).
3. Affect the activity of enzymes through the
messengers (cAMP). (Hormones that can not
penetrate the membrane).
4. 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 HYPOTHALAMUS
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.
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,
•somatostatin,
•corticoliberin,
•prolactostatin,
•foliliberin,
•melanostatin
•prolactoliberin,
•luteinising-hormone liberin,
•melanoliberin
 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 by somatoliberin, is

inhibited by somatostatin

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)
 Adrenoglomerulotro-
pin – 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
THYROID GLAND

Hormones of two
types:
 1. Iodine containing
: thyroxin
(tetraiodthyronin)
and triiodthyronin –
derivatives of
tyrosine;
 2. Calcitonin -
peptide
Synthesis of
iodine
containing
hormones is
regulated by
thyrotropic
hormone, which
in turn is
stimulated by
thyroliberin
 Functions of iodine containing
hormones

Necessary for
normal growth,
differentiation,
sex and mental
development

Regulate the
speed of
metabolism
 Effect on protein metabolism
In physiological concentration stimulate
synthesis of proteins, nucleic acids.
In the increased concentration activate
the protein decomposition.

Effect on carbohydrate metabolism

Accelerate the absorption of
carbohydrates in the intestine
Activate the decomposition of glycogen.
 Effect on lipid metabolism
Activate the exit of lipids from depot,
its decomposition and oxidation

Effect on energetic metabolism

In excess thyroxin uncouples
respiration and phosphorilation,
decreases the ATP formation and
increases the heat formation
Hyperfunction of gland –
diffuse toxic goiter
(thyrotoxicosis, Graves
disease)
•Goiter – hyperplasia of gland
•Hypermetabolism
•Increase of body
temperature
•Sweating, muscle weakness
•Weight loss with good
appetite
•Tremor, emotional lability,
insomnia
•Exophtalm
 Hypofunction of gland
(occurs in the deficit of
iodine in water, soil, air)
•Decrease of metabolism
•Decrease of body temperature mixedema

Hypofunction in childhood -
cretinism
cretinism
•Growth inhibition
•Unproportional body
development
•Disorders of mental
development

Hypofunction in adults –
mixedema
•Edema of mucosa
 Endemic goiter
(occurs in the
deficit of iodine in
water, soil and air)

Connective tissue is
enlarged in gland and
it is increased in size
markedly
 Calcitonin
 Is synthesized by
parafollicular cells of
thyroid gland

 Affects the metabolism of Са and Р

- Promotes the transferring of Са2+ from
blood into bones
- Inhibits reabsorption of Р in kidneys
(decreases the content of Р in blood due to
its excretion with urine)
 Increase of
calcitonin
- hypocalciemia
- hypophosphatemia
- hyperphosphaturia

 Decrease of calcitonin
- hypercalciemia
- hyperphosphatemia

- hypophosphaturia
 PARATHYROID GLANDS
Parathyroid hormone - protein

 Affects the metabolism

of Са and Р
- Promotes moving of Са2+
from bones into blood
- Inhibits reabsorption of Р
in kidneys (decreases the
content of Р in blood due  Дія зв’язана з вітаміном
to its excretion with D (утворює активну
urine) форму вітаміну D в
- Stimulates the absorption нирках)
of Ca in the intestine
  Hypofunction
 Hyperfunction - hypocalciemia
(Recklinghausen’s - hyperphosphatemia
disease) - hypophosphaturia
- hypercalciemia - tetanus
- hypophosphatemia
- hyperphosphaturia
- osteoporosis
- Accumulation of Са
in tissues
 EPINEPHRINE GLANDS
Two parts:
-cortex
-medulla
 Hormones of medulla -
catecholamines
 Epinephrine, norepinephrine and DOPA
 Nature – derivatives of tyrosine
 Excretion is regulated by sympathetic nervous
system and brain cortex
 Functions:
Stress hormones. Contraction of vessels, increase
the blood pressure, accelerate pulse. Contraction
of uterus muscles. Epinephrine relaxes the muscles
of bronchi and intestine.
On carbohydrate metabolism:
-activates the decomposition of glycogen in liver and
muscles
-activates glycolysis, PPC, TAC and tissue respiration
On protein metabolism
-accelerate the decomposition of proteins
On lipid metabolism
-activates lipase, mobilization of lipids and their
oxidation
 Hormones of cortex -
corticosteroids
 There are more than 50 corticosteroids
 Nature – steroids

 Are synthesized from cholesterol

 Two groups
-glucocorticoids (protein, carbohydrate and
lipid metabolism)
-mineralocorticoids (mineral metabolism)
 Glucocorticoids

Most important: corticosteron, cortison,

hydrocortison
Synthesis is regulated by ACTH
Are transported combined with proteins
Half-life time – till 1 hour
In the decomposition17-ketosteroids are
formed (excretion with urine). Diagnostic
significance – index of the function of
cortex of epinephrine glands and testis
 Functions

• Antiinflammatory, antiallergic, antiimmune

• Adaptive effect
• Maintain the blood pressure
• Maintain the volume of extracellular liquid
 Effect on protein metabolism

• Stimulate catabolic processes in

connective, lymphoid and muscle
tissues
• Activate protein synthesis in liver
• Stimulate amino transferases
• Stimulate the urine biosynthesis
 Effect on the carbohydrate
metabolism
Increase the glucose level
• Activate gluconeogenesis
• Inhibit hexokinase (glycolisis)

Effect on the lipid metabolism

• Activate lipolysis
• Activate the conversion of FA into
carbs
 Mineralocorticoids
The most important hormone: aldosteron
Excretion is controlled by rhenin-
angiothensin system
Functions:
-activate the
reabsorption of Na,
water and Cl in kidney
canaliculi
- Promotes the excretion
of К ions via the
kidneys, skin and saliva
 Disorders of the function of
epinephrine gland cortex
Insufficiency: Addison disease (bronze
disease)
Causes:
-injury of epinephrine gland cortex
-insufficient production of ACTH
Blood pressure
decrease, loss of
weight, weakness,
anorexia.
Hyperpigmentation -
bronze skin
 Hyperproduction: Kushing syndrom
Causes: hypeplasia or tumor of epinephrine
gland cortex
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
 Aldosterone hyperproduction
Causes:
-aldosteroma

Symptoms:
-hypokaliemia
-hypernatriemia
-hyperchloremia
-hypervolemia
-edema,
hypertension
 Sex hormones
Are synthesized in:
-sex glands
-placenta
-cortex of epinephrine
glands

A little amount of female sex hormones is

formed in male organism and vice versa.
Female – estrogens, progesteron.
Male – androgens.
 Estrogens
Nature: steroids
Estradiol – is formed in follicles of ovarium
Estron and estriol – are formed in liver and
placenta in the metabolism of estradiol

eстрадіол естріол
 Functions of estrogens
Development of the female reproductive system
organs
Ability to fertility in reproductive period

Biochemical functions of
estrogens
Anabolic action on the
tissues of reproductive
organs
Inhibit the exit of Ca
from bones
(osteoporosis in
menopause)
 Progesteron
Nature: steroid
Is formed in corpus luteum, placenta and
epinephrine glands
 Functions of progesteron
Prepares the endometrium of uterus to
implantation of ovum
Inhibits the uterus contraction during
pregnancy
Stimulates the growth of mammary glands
 Androgens
Testosteron
Nature: steroid
Is formed in the interstitial cells of testis
Is excreted as 17-кetosteroids
 Functions of testosterone
Development of the primary sex features
Development of the secondary sex
features
Stimulates spermatogenesis

Biochemical functions of testosterone

Strong anabolic action (stimulates the
synthesis of NA, proteins, phospholipids)
– increases the mass of muscles
Keeps the Ca and P in organism
Derivatives of androgens – active
anabolics