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Principles of metabolism regulation
Molecular mechanisms of hormonal signal transduction
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Secretory cell secretes a hormone into extracellular medium. A hormone binds to the same cell inducing physiological response.
Secretory cell is also a target for its own hormone
Ways of cell communicationAutocrine way of signal trunsduction
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There are several types of cells in an organ/tissue. Secretory cells release first messenger (hormone) into extracellular medium. First messenger can reach an adjacent cell and combine with its receptors
Ways of cell communicationParacrine way of signal trunsduction
Secretory cell
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Ways of cell communicationEndocine way of signal trunsduction
A cell secretes a chemical compound into blood. Blood transports this compound into tissues, where a compound combines with cells inducing physiological response. A chemical compound secreted into blood is first-messenger. In physiological terms, it is a hormone.An organ (tissue) upon which a hormone acts is considered as a target-organ(tissue).Cells of target organ/tissue contain receptors specific in regard to a hormone. Receptors =proteins.
Secretory cell
Target cell
Blood Hormone
Receptor
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Hypothalamic-hypophyseal axis is controled by neural imputs from CNS.Hypothalamic hormones act on cells of adenohypophysis. Cells of adenohypophysis are considered as first rank target cells. Hormones of adenohypophysis act on cells of peripheral endocrine glands. The cells of peripheral endocrine glands are second rank target cells. Hormones of peripheral endocrine glands act on cells of various tissues. These cells are ultimate targets or third rank of target cells.
Neuroendocrine system and its ranking
Precursors
Precursors
Precursors
Hypothalamus
Liberins,Activators
StatinsInhibitors
Adenohypophysis
Feedback inhibitionTropins
Peripheralendocrinegland
Hormone
Ultimate target
Response
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Feedback inhibition in neuroendocrine system
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Hypothetical model of target cellReceptors in plasma membrane
Complex of receptor and hormone
Nucleus
Plasma membrane
Cytosole
Receptors for calcitriol,thyroid hormonesand retinoic acid
Steroid
Receptor in cytosol
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Functional classification of plasma membrane
reseptorsReceptors linked to adenylate cyclase system. Cyclic adenosine monophosphate (cAMP) is second messenger.Receptors linked to phospholipase C system. Inositol triphosphate (IP3), diacylglycerol (DAG) ir Ca2+ are second messengers.Receptors with enzymatic properties: receptory tyrosine kinase and receptory guanylate cyclase.
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Hormone action via plasma membrane
receptors
These receptors are characteristic to all hormones soluble in water.The main steps of action: formation of H-R complex; synthesis of second messenger (second messenger is a regulatory molecule immediately produced in a target cell in response to hormone); alterations of activities of intracellular enzymes; physiological response.
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Receptor
-baltymas Adenilatciklazė
Proteinkinazė A
Neaktyvi
i
Hormone Receptor
G-protein Adenylate cyclase
Plasma membrane
Proteinkinase A
InactiveProteinkinase AactivePhosphorylase kinase
Inactive, dephosphorylatedPhosphorylase kinaseActive, phosphorylated
ATP ADP
Glycogenphosphorylase binactive dephosphorylated
Glycogenphosphorylase aative ATP ADP
Glycogen( n)
(Glucose-1-phosphate) n
cAMP-mediated breakdown of glycogen
Functioning of receptors linked
to adenylate cyclase
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Synthesis of cAMP
Adenylate cyclase
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cAMP decomposition
Phosphodiesterase
H2O
Inhibited by alkaloids, e.g. caffeine
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Hormones acting via cAMPGlucagonAdrenalin (activation β-adrenoreceptors results in cAMP increasing, but α2 –in increasing)CalcitoninVasopressin (ADH, antidiuretic hormone) if interacts with V2-type receptors in cells of distal tubules of kidney.
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G-proteins as mediators of R-enzyme interaction
Adenylate cyclase
H H
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Transduction of hormonal signal through phospholipase C system
HormoneReceptor G-protein
Phospholipase C Proteinkinase C
ER
Ca-calamodulincomplex
Secretoryvesicles
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Hormones acting via phospholipase C system
Adrenalin/noradrenalin (via α1-
adrenoreceptors)Vasopressin (ADH) via V1receptors (in smooth muscles cells of blood vessels)
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Enzymatic receptors. Hormones acting via enzymatic receptors
•Insulin•Somatotropin/ growth hormone (GH)•Insulin-like growth factors•Cytokins•Natriuretic peptides
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Receptors with tyrosine kinase activity: receptory
tyrosine kinaseEpidermal growth factorreceptor
Fibroblast growthfactor receptor
Cys
-dom
ens
Insulin receptor
Cys
-dom
ens
Imun
oglo
buli
ne d
omen
s
Tirosinkinase
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Guanylate cyclase
NUP
Guanylate cyclase
Guanylate cyclase
Guanylate cyclase
NUP
Guanylate cyclase
Guanylate cyclase
Receptors with guanylate
cyclase activity
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Synthesis of cGMP by guanylate cyclase
GTP cGMP
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Action of hormones via intracellular receptors
Intracellular receptors bind only water insoluble hormones (lipophilic ones: steroid-, thyroid hormones and retinoic acid).True second messengers are not produced. Receptors are located in cytoplasm and nucleus of target cells.
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Baltymas
Hormone action through intracellular receptors
Hormone irprotein complexs
Free hormone Plasma membrane
Nucleus
Branduolioreceptoriai
Citozolioreceptoriai
ŠŠB
ProteinResponse
Activation
Activation
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Hsp and receptor complexHeat shock protein
DNR binding site
Hormone
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Structure of receptor specific to lipophilic hormone
A/B C E
Length varies
Regulatory domainDNAbindingdomain
Nuclear targetingsequence
Hormone-bindingdomain
Functional areas
EA/B
D C