Download HORMONES

Φυσιολογία 1η διάλεξη
13/11/2009
Κάτια Καραλή
Ερευνήτρια Β, ΙΙΒΕΑΑ
CELL
TISSUE
ORGAN
Heart
Brain
stomach
ORGANISM
SYSTEM
CARDIOVASCULAR
NERVOUS
GASTROINTESTINAL
CELL COMMUNICATION
physical
electrical
chemical
neurotransmitters
hormones
Receptor
Signaling pathway
Gene transcription
FUNCTION
SERIAL ACTIVATION
COMBINED ACTIVATION and
INHIBITION
TRANSCIPTIONAL REGULATION
TRANSLATIONAL REGULATION
POSTTRANSLATIONAL MODIFICATION
CELL-TO-CELL COMMUNICATION
Modes of signal transduction between different cell types
Types of cellular
receptors
INTERACTION BETWEEN SIGNALING
PATHWAYS:
SIMILARITIES TO NEURAL NETWORKS?
A simple neural network. The activity of each neural unit
(shown as a circle) is determined by the unit's inputs.
The output of each unit is usually a nonlinear function of the unit's
inputs. Each connection between units has a particular strength,
or "weight," which is indicated by differences in thickness of the
connecting arrows.
A simple hypothetical signaling network. The network consists of six
receptors and three cytosolic protein kinases. Each receptor activates ( green
arrows) or inhibits ( black lines) kinase 1 or 2 or both by an unspecified
mechanism. Because signals converge onto kinase 3 (the output kinase),
this network will be maximally active only when specific
combinations of extracellular stimuli are present. Although this network is far
simpler than any likely to be found in a living cell, it could form part of a more
complex signaling pathway.
Schematic representation of cross-talk
between signaling pathways
PHYSIOME
The quantitative and integrated description of the
Functional behavior of the physiological state of an
individual or species.
The physiome describes the physiological dynamics
of the normal intact organism
Is built upon information and structure
(genome, proteome, morphome).
PHYSIOME
In its broadest sense,
the physiome should define relationships
from genome to organism and
from functional behavior to gene regulation.
The Physiome Project includes integrated models of
components of organisms, such as particular organs or
cell systems, biochemical or endocrine systems.
Physiome Project :
Compiles and provides a central repository of
databases, linking experimental information and
computational models into a single,
self-consistent framework.
-----> it aims to promote comprehensive databases
and an integrative,
analytical approach to the study of medicine.
BODY SYSTEMS
Skeletal and Muscle
Gastrointestinal (Digestive)
Circulatory and Respiratory
Urinary
Reproductive
Nervous
Endocrine
HOMEOSTATIC MEDIATORS
Hormones
Cytokines
Neurotransmitters
Growth
Factors
NUCLEAR RECEPTORS
Early response
Delayed response
THE NUCLEAR RECEPTORS SUPERFAMILY
Glucocorticoid Receptor
Signaling
Ligand
Cell Membrane
Ligand Binding
GR
Import
HSPs
Nucleus
Transactivation
/Transrepression
Assembly
TF
Export
GREs
mRNA1
TFE
mRNA2
Transcriptional Activation by GR
through Interaction with Multiple
Protein Complexes
SWI/SNF
Histone
Acetyltransferases
DRIP/TRAP
p300/CBP
p/CAF
p160
Transcription initiation
complex
AF2
AF1
GR GR
Coactivation
RNA
polymerase II
AF1
Chromatin modulation
GREs
Transcription
Non – nuclear receptor families
MODES OF SIGNALING
Typical structure of a G-protein coupled receptor (GPCR)
C. Enzyme-linked receptors
IL-2: an example of a cytokine receptor
Schematic representation of cross-talk
between signaling pathways
MOLECULAR MEDIATORS OF ENERGY
HOMEOSTASIS
Neuropeptides
* Agouti protein
* a-MSH (a-Melanocyte stimulating hormone)
* Cocaine- and amphetamine –regulated transcript (Cart)
* Hypocretin (or Orexin) 1 and 2
* MCH (melanin-concentrating hormone)
* NPY (neuropeptide Y)
* TRH (thyrotropin-releasing hormone)
Peripheral molecules
* Leptin
* CCK (cholecystokinin)
* Ghrelin
* Insulin
Combination of a receptor with the
hormone (ligand) leads to activation of
adenylate cyclase bound also to the
membrane.
Increased activity of adenylate cyclase
increases cAMP in the cytosol.
cAMP acts inside the cell to alter the rate
of process(es).
Endocrine system
Hormones are synthesized by glands
Secreted directly into the blood and carried
to their sites of action
Specifically alter the activities of responsive tissues
HORMONES:
Chemical substances liberated by
specific cell types carried by the
bloodstream to act on distant target cells.
The cell membrane contains
receptors for hormones.
Central Nervous System
Stimuli
HYPOTHALAMUS
Releasing hormone
pituitary
Trophic hormone
PERIPHERAL
GLAND
Hormone
PHYSIOLOGICAL ACTIONS
HYPOFUNCTION
Destruction block
HYPERFUNCTION
GLAND
prohormone
block
stimulation
HORMONE
DEGRADED
ANTIBODIES
ANTAGONISTS
Tumor hyperplasia
Ectopic production
block
DEGRADED
receptor
ANTIBODIES
STIMULATION
DEFECT
effector
response
TISSUE
DAMAGE
Target cell
Early thoughts: neuronal contributions to various bodily
functions could be localized to discrete brain regions
or centers.
Experiment (1940s): lesioning of the brain
and evaluation of physiology following the distruction
of specific areas.
-bilateral lesioning of LHA  anorexia and weight loss
-bilateral lesioning of VMN  obesity
In the hypothalamus:
LHA controls hunger
VMN controls satiety
Two classes of neurons involved in
responses to leptin in the CNS:
-depolarized-> anorexigenic peptides
-hyperpolarized->orexigenic peptides
Npy
increased by starvation
not regulated by overfeeding
Pomc / Cart
increased by starvation
decreased by overfeeding
Leptin : an adipose tissue secreted
hormone; the product of the ob gene.
Its main physiological role is to signal
nutritional status during periods of
food deprivation
Insulin and leptin:
Circulate at levels proportional to body fat
content
Enter the CNS in proportion to their plasma level
Their respective receptors are expressed in
neurons involved in energy intake
Administration of either icv reduces food intake
Deficiency of either or components of their
signaling pathway increases food intake
The above strongly support their function as
adiposity signals.
Genes
Monogenic disorders
Susceptibility genes
OBESITY
Metabolic rate
Exercise
Food intake
Culture
Cardiovascular
Endocrine
Gastrointestinal
Nervous