GENERAL PRINCIPLES OF METABOLISM REGULATION.

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GENERAL PRINCIPLES OF METABOLISM REGULATION.
HORMONES.
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Levels of the homeostasis regulation
Highest level nervous system
Intermediate - hormonal regulation
Intracellular (enzymes)
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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) enter blood and
regulate processes on the organism level.
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• Specific stimulus for hormones secretion is
• nervous impulse
• concentration of the certain compound in blood
  passing through the endocrine gland

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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
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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 lands, sex hormones.
5. Derivatives of polyunsaturated fatty
   (arachidonic) acids prostaglandins.

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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)

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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
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• 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

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Model of the insulin receptor ( Jacobs,
Cautrecasas, 1982)  
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• 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

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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).

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HYPOTHALAMUS
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.
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Tight anatomical bonds with pituitary gland
Two groups of hormones related to anterior and
posterior lobes of pituitary
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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 vasopressina
   and oxytocin into pituitary gland)

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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
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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

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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
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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.
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Acts both directly and through the stimulation of
the formation of polypeptides somatomedins
(insulin-like growth factors). ILGF are
synthesized in liver
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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.

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In the inherited hypoplasia of pituatary gland
dwarfism is developed. For the treatment GH is
used.
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Hyperproduction of GH before puberty and before
the completion of ossification results in
gigantism
Yao Defen, the tallest women in the life, 2.36 ?
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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
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Adrenocorticotropic hormone (?CTH)

• 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

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Cushings 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
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Thyrotropic hormone (??H)

• 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

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Gonadotropic hormones
Follicle-stimulating ??????
Chemical nature protein (glycoprotein) Secretio
n 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 n women and
secretion of testosterone in men
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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
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Lipotropic hormones
Chemical nature simple proteins Functions
-mobilization of lipids from depot -melanocyte
stimulating function -decrease Ca in blood
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THE INTERMEDIATE LOBE OF PITUITARY
Melanocyte stimulating hormone (melanotropin)
Chemical nature peptide Functions -stimulates
melaninogenesis -adaptation of vision in darkness
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POSTERIOR LOBE OF PITUITARY
Vasopressin (antidiuretic hormone)
Chemical nature peptide
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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 Insufficie
ncy diabetes insipidus (polyuria, low density
of urine, dehydratation)
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Oxytocin
Chemical nature peptide
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• 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

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• EPIPHYSIS (PINEAL GLAND)
• Produces
• ?elatonin 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

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PANCREAS
Exocrine and endocrine parts Endocrine
Langerhans islets (alpha-, beta- and
delta-cells)
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Alpha-cells glucagon Beta-cells
insulin Delta-cells somatostatin Epithelium of
ducts lipocain
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Insulin

• Nature protein (51 ?A)
• Is formed from proinsulin by proteolisis
• Contains zinc

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• 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

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• 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-?etoglutarate
  dehydrogenase
• Inhibits gluconeogenesis
• Inhibits the decomposition of glycogen
  (glucose-6-phosphatase)

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• 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-??P-?se

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Glucagon

• Nature polypeptide
• Antagonist of insulin
• Synthesis is activated in fasting

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• Functions
• Activates the decomposition of glycogen in liver
• Activates gluconeogenesis
• Inhibits glycolysis
• Activates lipolysis

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Somatostatin

• Nature peptide
• Functions
• Inhibits secretion of insulin and glucagon
• Inhibits secretion of STH and TTH
• Inhibits secretion of local hormones of intestine

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Lipocain

• Functions
• Activates the synthesis of phospholipids in liver
• Stimulates the action of lipotropic factors
• Activates the oxidation of fatty acids in liver

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THYROID GLAND

• Hormones of two types
• 1. Iodine containing thyroxin
  (tetraiodthyronin) and triiodthyronin
  derivatives of tyrosine
• 2. Calcitonin - peptide

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Synthesis of iodine containing hormones is
regulated by thyrotropic hormone, which in turn
is stimulated by thyroliberin
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• Functions of iodine containing hormones

Necessary for normal growth, differentiation, sex
and mental development Regulate the speed of
metabolism
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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.
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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
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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

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Hypofunction of gland (occurs in the deficit of
iodine in water, soil, air)

• Decrease of metabolism
• Decrease of body temperature
• Hypofunction in childhood - cretinism
• Growth inhibition
• Unproportional body development
• Disorders of mental development
• Hypofunction in adults mixedema
• Edema of mucosa

mixedema
cretinism
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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
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Calcitonin

• Is synthesized by parafollicular cells of thyroid
  gland

• Affects the metabolism of ?? and ?
• Promotes the transferring of ??2 from blood into
  bones
• Inhibits reabsorption of ? in kidneys (decreases
  the content of ? in blood due to its excretion
  with urine)

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• Increase of calcitonin
• hypocalciemia
• hypophosphatemia
• hyperphosphaturia

• Decrease of calcitonin
• - hypercalciemia
• hyperphosphatemia
• hypophosphaturia

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PARATHYROID GLANDS
Parathyroid hormone - protein

• Affects the metabolism of ?? and ?
• Promotes moving of ??2 from bones into blood
• Inhibits reabsorption of ? in kidneys (decreases
  the content of ? in blood due to its excretion
  with urine)
• Stimulates the absorption of Ca in the intestine

• ??? ??????? ? ????????? D (??????? ??????? ?????
  ???????? D ? ??????)

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• Hypofunction
• hypocalciemia
• hyperphosphatemia
• hypophosphaturia
• tetanus

• Hyperfunction (Recklinghausens disease)
• hypercalciemia
• hypophosphatemia
• hyperphosphaturia
• osteoporosis
• Accumulation of ?? in tissues

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EPINEPHRINE GLANDS
Two parts -cortex -medulla
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Hormones of medulla - catecholamines

• Epinephrine, norepinephrine and DOPA
• Nature derivatives of tyrosine
• Excretion is regulated by sympathetic nervous
  system and brain cortex

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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 -accelera
te the decomposition of proteins On lipid
metabolism -activates lipase, mobilization of
lipids and their oxidation
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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)

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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
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• Functions
• Antiinflammatory, antiallergic, antiimmune
• Adaptive effect
• Maintain the blood pressure
• Maintain the volume of extracellular liquid

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• 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

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• 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

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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 ? ions via the kidneys, skin and
saliva
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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
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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
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Aldosterone hyperproduction Causes
-aldosteroma
Symptoms -hypokaliemia -hypernatriemia -hyperchlo
remia -hypervolemia -edema, hypertension
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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.
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Estrogens Nature steroids Estradiol is formed
in follicles of ovarium Estron and estriol are
formed in liver and placenta in the metabolism of
estradiol
???????
e????????
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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)
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Progesteron Nature steroid Is formed in corpus
luteum, placenta and epinephrine glands
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Functions of progesteron Prepares the endometrium
of uterus to implantation of ovum Inhibits the
uterus contraction during pregnancy Stimulates
the growth of mammary glands
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Androgens Testosteron Nature steroid Is formed
in the interstitial cells of testis Is excreted
as 17-?etosteroids
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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
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Derivatives of androgens active anabolics