Transcript Neuroendokrininės sistemos hierarchija

Principles of metabolism
regulation
Molecular mechanisms of
hormonal signal transduction
Ways of cell communication
Autocrine way of signal trunsduction
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 communication
Paracrine way of signal trunsduction
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
Secretory cell
Ways of cell communication
Endocine 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.
Target cell
Secretory cell
Blood
Receptor
Hormone
Neuroendocrine system and its ranking
Precursors
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.
Hypothalamus
Statins
Inhibitors
Liberins,
Activators
Precursors
Adenohypophysis
Tropins
Feedback inhibition
Precursors
Peripheral
endocrine
gland
Hormone
Ultimate target
Response
Feedback inhibition in
neuroendocrine system
Hypothetical model of target cell
Receptors in plasma
membrane
Complex of receptor
and hormone
Nucleus
Plasma membrane
Cytosole
Receptors for calcitriol,
thyroid hormones
and retinoic acid
Steroid
Receptor in cytosol
Functional classification of
plasma membrane reseptors
Receptors 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.
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.
Hormone Receptor
Plasma membrane
-baltymas
G-protein
Adenilatciklazė
Adenylate
cyclase
Functioning of
receptors linked to
adenylate cyclase
Proteinkinazė A
Proteinkinase
A
Neaktyvi
Inactive
Proteinkinase A
i
active
Phosphorylase kinase
Phosphorylase kinase
Inactive, dephosphorylated
Active, phosphorylated
ATP ADP
Glycogenphosphorylase b
inactive dephosphorylated
cAMP-mediated
breakdown of glycogen
Glycogenphosphorylase a
ATP ADP
ative
Glycogen( n)
(Glucose-1-phosphate) n
Synthesis of cAMP
Adenylate cyclase
cAMP
decomposition
Phosphodiesterase
H2O
Inhibited by alkaloids, e.g. caffeine
Hormones acting via cAMP
Glucagon
Adrenalin (activation β-adrenoreceptors
results in cAMP increasing, but α2 –in
increasing)
Calcitonin
Vasopressin (ADH, antidiuretic hormone) if
interacts with V2-type receptors in cells of
distal tubules of kidney.
G-proteins as mediators of Renzyme interaction
H
H
Adenylate cyclase
Transduction of hormonal signal through
phospholipase C system
Receptor
Hormone
G-protein
Phospholipase C Proteinkinase C
Ca-calamodulin
complex
ER
Secretory
vesicles
Hormones acting via phospholipase C
system
Adrenalin/noradrenalin (via α1adrenoreceptors)
Vasopressin (ADH) via V1receptors (in
smooth muscles cells of blood vessels)
Enzymatic receptors. Hormones
acting via enzymatic receptors
•Insulin
•Somatotropin/ growth hormone (GH)
•Insulin-like growth factors
•Cytokins
•Natriuretic peptides
Receptors with tyrosine kinase
activity: receptory tyrosine
kinase
Imunoglobuline
domens
Fibroblast growth
factor receptor
Cys-domens
Cys-domens
Epidermal growth factor
Insulin receptor
receptor
Tirosinkinase
Guanylate cyclase
Guanylate cyclase
NUP
Guanylate cyclase
Receptors with
guanylate cyclase
activity
Synthesis of cGMP by
guanylate cyclase
GTP
cGMP
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.
Hormone action through intracellular
receptors
Hormone ir
protein
complexs
Free hormone
Plasma membrane
Nucleus
ŠŠB
Branduolio
receptoriai
Citozolio
receptoriai
Activation
Activation
Response
Baltymas
Protein
Hsp and receptor complex
Heat shock protein
DNR binding site
Hormone
Structure of receptor specific to lipophilic
hormone
Length varies
Functional areas
A/B
Regulatory domain
E
C
DNA
binding
domain
E
D
Nuclear targeting Hormonebinding
sequence
domain
A/B
C