hormones. mechanism of regulatory effectsdo.rsmu.ru/fileadmin/user_upload/lf/hormones_1.pdf ·...
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Hormones. Mechanism of
regulatory effects
prof. Davydov V.V.
Department of biochemistry and molecular biology
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Hormones refers to biologically active substances
which are synthesized in endocrine glands, secreted into
the bloodstream and have a regulatory effect on the
metabolism and function of certain visceral organs.
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Role of hormones:
- take part in the integration of metabolism in the
various tissues in the human body;
- take part in the adaptation of metabolism to effect of
adverse factors
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Classification of hormones
• hypothalamic hormones (liberins, statins);
• anterior pituitary hormones (adrenocorticotropic hormone –
ACTH, growth hormone, follicle stimulating hormone, luteinizing
hormone, luteotropic hormone, thyroid stimulating hormone);
• posterior pituitary hormone (vasopressin, oxytocin);
• thyroid hormones (thyroxine, triiodothyronine, calcitonin);
• parathyroid hormone (PTH);
• pancreatic hormones (insulin, glucagon);
• hormones of adrenal cortex (glucocorticoids, mineralocorticoids)
and adrenal medulla (epinephrine);
• sex hormones (testosterone, estradiol);
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Membrane receptor
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Cytoplasm receptor
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Mechanism regulatory effects of hormones which
bind with intracellular (cytoplasmic) receptors
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Mechanism regulatory effects of hormones which
bind with membrane receptors
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Classification of hormones which bind with
membrane receptors
№ hormone effector
protein
second
massager
1 ACTH, ТТH,
calcitonin,
glucagon,
epinephrine, FSH,
LH, MSH
adenylate
cyclase
cAMP
2 atrial nairiuretic
peptide
guanylate
cyclase
cGMP
3 Vasopressin (V1),
gastrin, tyroliberin,
gonadoliberin
phospholipase
С
1,2-diacylglycerol,
inositol 1,4,5-
triphosphate, Са2+
4 insulin,
oxytocin
- -
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Mechanism of regulatory effect of hormones
which effect are mediated by activation of
adenylate cyclase
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Structure of β2–adrenergic receptor
(serpentine receptor)
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Mechanism of regulatory effect of hormones
which effect are mediated by activation of
adenylate cyclase
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Scheme of G-protein transformations
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Mechanism of regulatory effect of hormones
which effect are mediated by activation of
adenylate cyclase
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cАMP
N
NN
N
NH2
O
OH
CH2O
O
P
OH
O
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Mechanism of activation of protein kinase A by cAMP
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Protein phosphorylation by protein kinase A
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Enzymes which are regulated by cAMP-dependent
phosphorylation
Enzyme Pathway
Glycogen synthase
Kinase phosphorylase
Pyruvate kinase
Phosphofructokinase
Pyruvate dehydrogenase
complex
Hormone sensitive lipase
Fructose 1,6-bisphospha-
tase
CREB (cAMP response
element-binding protein)
– factor of transcription
Glycogen synthesis
Glycogenolysis
Glycolysis
Glycolysis
Oxidative decarboxylation of
pyruvate
Lipolysis
Gluconeogenesis
CRE of DNA – take part in
the regulation of gene
expression
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Mechanism of regulatory effect of hormones
which effect are mediated by activation of
adenylate cyclase
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Classification of adrenoreceptors
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Effect of cholera toxin
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Effect of pertussis toxins
дифтерия
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Classification of hormones which interact with
membrane receptors
№ hormone effector
protein
second
massager
1 ACTH, ТТH,
calcitonin, glucagon,
epinephrine, FSH,
LH, MSH
adenylate
cyclase
cAMP
2 atrial nairiuretic
peptide
guanylate
cyclase
cGMP
3 vasopressin,
gastrin, thyroliberin,
gonadoliberin
phospholipase
С
1,2-diacylglycerol,
inositol 1,4,5-
triphosphate, Са2+
4 insulin,
oxytocin
- -
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Mechanism formation of the cellular response to
the vasopressin
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Reaction, which are catalyzed by phospholipase C
CH2O-CO-R
CHO-CO-R1
CH2
O
POH O
O
OHOH
OH OPO3H
2
OPO3H
2
CH2O-CO-R
CHO-CO-R1
CH2
OH
OPO3H
2
OHOH
OH OPO3H
2
OPO3H
2
H2O+
PL C+
phosphatidyl inositol
4,5-bisphosphate
1,2-diacylglycerol
(DAG) inositol
1,4,5-triphosphate
(IP3)
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Mechanism formation of the cellular response to
the vasopressin
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Complex calcium-calmodulin
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Some intracellular proteins regulated by calcium-
calmodulin complex
Adenylate cyclase
Glutamate decarboxylase
Myosin light chain kinase
Nitric oxide synthase
Ca-ATPase (Ca2+-pump
of membranes)
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Mechanism formation of the cellular response to
the vasopressin
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Classification of hormones which interact with
membrane receptors
№ hormone effector
protein
second
massager
1 ACTH, ТТH,
calcitonin, glucagon,
epinephrine, FSH,
LH, MSH
adenylate
cyclase
cAMP
2 atrial nairiuretic
peptide
guanylate
cyclase
cGMP
3 vasopressin,
gastrin, thyroliberin,
gonadoliberin
phospholipase
С
1,2-diacylglycerol,
inositol 1,4,5-
triphosphate, Са2+
4 insulin,
oxytocin
- -
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Receptor to ANP
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Guanylate cyclase reaction
O
N
N
N
N
OH
OH
CH2O
O
P O
OH
NH2
cGMP
GTP + H2O cGMP + H4P2O7
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Tyrosine kinase mechanism
effect of hormones
1. Activation of receptor
2.Phosphorylation proteins
3. Activation of MAP kinases
or STAT kinases
4. Activation of genes
expression in nucleus
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Thanks for your listening!