Download Lecture # 15: The Endocrine System 2

The Endocrine System (Chapter 17)
Lecture # 15: The Endocrine System 2
Objectives
1- To identify the chemical classes
to which various hormones belong.
2- To describe how hormones
stimulates their target cells.
Hormone Chemistry
Most hormones fall into three chemical classes:
1- Steroids: They are derived from cholesterol.
2- Peptides and Glycoproteins: They are chains of 3 to 200 or
more aminoacids.
3- Monoamines (biogenic amines): They are made from aminoacids
and retain an amino group.
1- Steroids:
They are secreted by gonads and adrenal
glands.
Estrogens,
progesterone,
testosterone,
cortisol, corticosterone, aldosterone, DHEA,
and calcitriol are steroid hormones.
Steroid hormones are derived
from cholesterol.
2- Peptides and Glycoproteins
They are created from chains of amino acids. They are secreted by
pituitary and hypothalamus.
Oxytocin, antidiuretic hormone, releasing and inhibiting hormones, and
anterior pituitary hormones.
3- Monoamines (biogenic amines)
They are derived from amino acids and secreted by adrenal, pineal,
and thyroid glands.
Epinephrine, norepinephrine, melatonin, and thyroid hormone are
mono-amines.
Aminoacid
Hormone Receptors and Mode of Action
Hormones stimulate only those cells that have receptors for them.
Receptors are protein or glycoprotein molecules on plasma
membrane, in the cytoplasm, or in the nucleus.
Usually each target cell has a few thousand receptors for a given
hormone.
Receptors act like switches turning on metabolic pathways when
hormone binds to them.
Metabolic effects can be achieved by different mechanisms:
1- Activation of genes in the nucleus to initiate the transcription and
synthesis of some proteins.
2- Activation of specific enzymes that are inactive in the cytosol.
3- Changes in the membrane permeability and membrane potentials.
1- Activation of genes in the nucleus to
initiate the transcription and synthesis of
some proteins.
2- Activation of specific enzymes that
are inactive in the cytosol.
Protein kinases are proteins present
in the cytosol as inactive proteins.
When protein kinases are activated
they have the ability to activate
many other enzymes.
3- Changes in the membrane permeability
and membrane potentials.
Hormone Receptors and
Mode of Action
Free hormones
(hydrophilic)
Receptor in plasma
membrane
Transport
protein
Bound hormones
(hydrophobic)
Secondmessenger
activation
Target
cell
Tissue
fluid
Hydrophilic Hormones
(Peptides and
Catecholamines)
1- They cannot penetrate into
target cell.
2- They must stimulate target
cell physiology indirectly.
Receptor in
nucleus
Hydrophobic Hormones (Steroids
and Thyroid hormones)
1- They penetrate plasma membrane and enter nucleus.
Blood
2- They act directly on the genes changing target cell
physiology.
3- It takes several hours to days to show effect due to
lag for protein synthesis.
Action of Hydrophobic Hormones
The Action of Thyroid Hormone on a Target Cell
Thyroxine
Binding
Globulin
1- Thyroid hormone enters target
cell by diffusion – mostly as T4 with
little metabolic effect.
2- Within target cell, T4 is converted
to more potent T3.
3- T3 enters target cells and binds to
receptors in chromatin and activates genes.
4- Activated genes make a muscle
protein (myosin) enhancing cardiac
muscle response to sympathetic
stimulation
and
strengthening
heartbeat.
5- Activated genes also make the
enzyme Na+ - K+ ATPase. One of its
effects is to generate heat, thus
accounting for the calorigenic effect
of thyroid hormone.
Action of Hydrophilic Hormones
The hormone binds to a cell-surface receptor, which is linked to a
second messenger system on other side of the membrane.
Second messengers:
1- cAMP produced by the enzyme adenylate cyclase.
2- Diacylglycerol (DAG) and Inositol triphosphate (IP3) produced by the enzyme
phospholipase.
The enzymes adenylate cyclase and phospholipase are integral proteins of
the plasma membrane of target cells.
Cyclic AMP as a Second Messenger
Hormone
G proteins and Hormone Activity
Hormone
They are the first messengers
that bind to receptors and leading
to the appearance of a second
messenger.
Receptor
They are glycoproteins of the
plasma membrane that bind
specific hormones and determine
the cell’s hormonal sensitivity.
Hormone
Receptor
Receptor
G protein
(activated)
(inactive)
Adenyl
cyclase
(activated)
(inactive)
ATP
G protein
It is an enzyme complex coupled
to the plasma membrane, which
is activated by the receptorenzyme complex. Once it is
activated, it activates the adenyl
cyclase.
cAMP
Adenylate
cyclase
Protein
kinase
(activated)
(Inactive)
cAMP
Opens ion
channels
Activates
enzymes
Protein
kinase
It is an enzyme that converts the
ATP in cyclic AMP (cAMP)
It is the second messenger that
activates the enzymes protein
kinases.
They are enzymes that perform
phosphorylations that activates
or inactivates other enzymes
Cyclic AMP as a Second Messenger
1 Hormone–receptor binding activates
a G protein.
2 G protein activates adenylate cyclase.
3 Adenylate cyclase produces cAMP.
4 cAMP activates protein kinases.
kinases
phosphorylate
5 Protein
enzymes.
This activates some
enzymes and deactivates others.
enzymes
catalyze
6 Activated
metabolic reactions with a wide
range of possible effects on the cell.
Metabolic reactions:
Synthesis
Secretion
Change membrane potentials
Diacylglycerol (DAG) and Inositol Triphosphate (IP3) as
Second Messengers
1
A hormone binds to its receptor,
which activates a G protein.
2
The G protein migrates
phospholipase
molecule
activates it.
3
The phospholipase transforms a
phospholipid molecule into DAG.
4
DAG activates a protein kinase, an
enzymes that phosphorylates other
enzymes with various metabolic
effects.
to a
and
1
A hormone binds to its receptor, which
activates a G protein.
2
The G protein migrates to a phospholipase
molecule and activates it.
3
The
phospholipase
transforms
phospholipid molecule into IP3.
a
The IP3 raises calcium concentration in the
cytosol in 2 ways:
6
1- IP3 opens gated channels in the plasma
membrane.
7
2- IP3 opens gated channels in the endoplasmic reticulum.
Calcium is a Third Messenger that can
have three effects:
8
Calcium may bind to other gated
membrane
channels
and
alter
the
membrane potential of the cells.
9
Calcium
may
activate
cytoplasmic
enzymes that alter cell metabolism.
10
Calcium may bind to the protein
Cadmodulin, which activates a protein
kinase.
Ca2+