MOLECULAR ENDOCRINE

DEPARTEMENT OF PHYSIOLOGY

SUMATERA UTARA UNIVERSITY

2006

Definision of the Endocrine

system
The endocrine system is
a collection of glands
and organs that produce
and regulate hormones
in the bloodstream to
control many functions
of the body.

ENDOCRINE SYSTEM

Uses chemical signals for cell to cell

communication
Coordinates the function of cells
Response to an endocrine signal
occurs within minutes to hours

Glands
A gland is a group of cells
that produces and
secretes, or gives off,
chemicals. A gland selects
and removes materials
from the blood, processes
them, and secretes the
finished chemical product
for use somewhere in the
body. Some types of
glands release their
secretions in specific
areas.

Hormones
A hormone is a chemical
produced in the body that
interacts with a receptor in a
target tissue to cause a change
in the function of that tissue.
There are various types of
hormones in the body and
include the exocrine (glands
with ducts that release
hormones for local action), and
endocrine hormones.hormones
carry messages from glands to
cells to maintain chemical levels
in the bloodstream that achieve
homeostasis.

ENDOCRINE GLAND
release

HORMON

TARGET CELL

PHYSIOLOGY RESPONS

HYPOTHALAMUS
TRH

GnRH
CRH

DA
GHRH/GHIH

HIPOFISE ANTERIOR
+
+
+

TSH

FSH/LH
ACTH

Ovary/Testes

+
Adrenal Cortex

ADH

HIPOFISE POST

PRL

OXY

Breast

ADH

GH
+

Thyroid

OXY

Breast
All Tissues

Kidney

Hormon as mediator

Hormon as the same as neurotransmitter act as first

messenger
Binding with receptor of target cells and influence
second messenger to give effect of the target cells,
create physiological respons
Only hydrophilic hormon needs first messenger
Lipophilic hormon go directly into target cell and
involve in DNA/RNA transcription form new protein

cell communication

Hormon Classification

Based on its substance:

Peptide and poly protein (TSH, Insulin, Parathyroid
hormone)
Amine (Thyroid hormone, epinephrine)
Steroid (cortisol, aldosterone, testosterone)

Based on receptor location in target cells :

Hydrophilic
Lipophilic

HORMONE CLASSIFICATION
(Based on the substance)
STEROID

NON STEROID:
- AMINE
- PROTEIN AND
POLYPEPTIDE

Hormone Classification
Proteins-thyroid stimulating hormone,
insulin, parathyroid hormone
Amino acids-thyroid hormone,
epinephrine
Steroids-cortisol, aldosterone,
testosterone

Based On their receptor location

HYDROPHILIC PEPTIDES AND CATHECOLAMINE
- Poorly soluble in lipid
- Cannot through lipid membrane barrier
- Binding with spesific receptor on the outer suface of
plasma membrane
LIPOPHILIC STEROID & THYROID HORMONE
- Easily pass through the surface membrane
- Binding with specific receptor inside the targe cell

Non-Steroid Hormones are secreted from both

the thyroid and adrenal glands.

Unlike steroid hormones, non-steroid hormones

cannot directly cross the cell membrane.

They regulate many functions including

growth, hunger, thirst, and sex drive.

Steroid Hormones are derived from

cholesterol and secreted from the
adrenal glands, testis, and ovaries.

They are Lipids which means that they can

cross cell membranes easily.
They stimulate cell growth and
differentiation and regulate the synthesis
of specific proteins.

Both steroid and non-steroid hormones enter the bloodstream

after being secreted by the endocrine glands.
They travel to other parts of the body where they locate specific
cells called target cells.

Target cells are cells that have receptors for specific

hormones.
Steroid hormones and non-steroid hormones have different ways
of entering the target and both have separate types of target cells
that they enter.

Hormone Receptors (cont)

Receptors are classified by their locations

1) Membrane receptors - Embedded in the cell membrane
Span the phospholipid bilayer
Hormone binds extracellularly
Binding alters receptor conformation, transmits
intracellular signal (those famous G-proteins!)
2) Cytosolic and nuclear receptors - in the cytoplasm or
nucleus (genomic)
Activated receptor binds to DNA and initiates/alters
gene transcription
Hormone must enter cell first

Receptor
Ligand

binding specificity
Effector specificity (signalling pathway)
Note
- Different receptor with different effector
specificity can bind the same ligand
- Different receptor with different binding
specificity may have the same effector
specificity

AMINE HORMONE
Derived from the amina acid tyrosine
Includes thyroid hormones and catecholamines
Stored until secreted
Receptor intra celluler and outer surface

Protein and Polypeptide Hormones:

Synthesis and Release

Figure 7-3: Peptide hormone synthesis, packaging, and release

Protein and Polypeptide Hormone Receptors

Surface receptor
Hormone binds
Transduction
Enzyme activation
Open channels
Second messenger
systems
Synthesis
Figure 7-5: Membrane receptors for peptide hormones

Steroid Hormones
Cytoplasmic or nuclear receptors (mostly)
Activate DNA for protein synthesis
Slower acting, longer half-life
Examples: cortisol, estrogen & testosterone

Steroid Hormones: Action

Figure 7-7: Steroid hormone action

What is a second messenger?

An intracellular signalling molecule

whse
concentrarion increases (or decreases) in response
to binding of an extracellular ligand to a cell surface
receptor

Second messengers for hormone are :

cAMP, cGMP, IP3, DAG, and Ca2+

Second messengers

Hormone stimulation of Gs protein-coupled receptors

(GPCRs) leads to activation of adenylyl cyclase and
synthesis of the second messenger cAMP
cAMP does not function in signal pathways initiated
by receptor tyrosine kinases (RTKs), but other second
messengers may be initiated by both GPCRs and
RTKs
cAMP and other second messengers activate specific
protein kinases
cAMP specifically activates cAMP-dependent protein
kinases (cAPKs)

The effects of many hormones are

mediated by second messengers

Ca2+
Structural formulas of four common intracellular second messengers.
Their abbreviations are indicated.

2nd messengers

2nd messengers
-cAMP
-IP3 and DAG
-calcium

kinases
transcription facto
gene expression

what is signal transduction?

Conversion of a signal from one physical or
chemical form into another.
In cell biology, it commonly refers to the sequential
process initiated by binding of an extracellular
signal to a receptor and culminating in one or more
specific cellular responses.

Protein Laboratory, University of Copenhagen

-Protein kinases
-Protein phosphatases
-Compartmentalization by
clustering
(lipid rafts/DRD/caveolae)
and scaffolding

Cyclases and phosphodiesterases,

Protein kinases and phosphatases
ATP

cAMP

GTP

cGMP

adenylyl cyclase

guanylyl cyclase

AMP

cAMP phosphodiesterase

GMP

cGMP phosphodiesterase

Protein o ATP protein

kinase
Protein * P ADP
Protein * P protein
phosphatas
e Protein o Pi
cAMP can activate proteins directly, e.g.
PKA, cAMP-gated channels, etc.
ATP can donate P to phosphorylate protein
Phosphatases turn off the signal

Signal Transduction
Endocrine, paracrine, and autocrine
signals.

Sequence
1.
Ligand-receptor binding

Signal (first messenger - extracellular)

Receptor

Signal transduction

2.

Transducer (across membrane)

Amplifier (enzyme)
Second messenger (cytoplasmic)
Second messenger target (PK)
Downstream targets

3. (Cytoplasmic) cellular response and/or

4. (Nuclear) change in gene expression

Types of Cell Signaling

Direct cell-cell signaling vs.

signaling via secretion

Types of Cell Signaling

Cell surface
receptors vs.
Intracellular
receptors

Types of Cell Signaling

Three forms of signaling by secreted

molecules

Paracrine
Synaptic
Endocrine

GAP JUNCTION

Chemical Signals
(Primary messengers)

Are diverse: can be amino acids/derivatives,

peptides, proteins, fatty acids, lipids,
nucleotides/derivatives.
Water soluble ligands bind to plasma
membrane receptors.
Lipid soluble ligands diffuse across the MB,
bind to intracellular receptors.

Receptors
Types of receptors:

Ion-channel-linked (ligand-gated channels)

Plasma membrane G protein-linked
Plasma membrane enzyme-linked
Intracellular, e.g. steroid hormone receptors

Binding of ligand causes:

change in conformation
clustering of receptors/endocytosis
signal transduction across the membrane

Desensitization results from chronic exposure to a ligand, due

to down-regulation of the receptor.

Removal of receptor from membrane

Alteration to receptor to lower its affinity for ligand
Alteration to receptor so that signal cant be transduced
Can also lead to drug tolerance, so same effect is not achieved from
same dose (e.g. nasal sprays)

Plasma MB receptors: G-Protein

linked

Trimeric G proteins are

Molecular Switches

Happens quickly

cAMP pathway
cAMP

Protein kinase A

ATP + Pro ADP + Pr*-PO3

(Phosphorylation
of target proteins)

Cellular response

Protein Kinase A (PKA)

PKA composed of 2
regulatory, 2 catalytic
subunits
cAMP binds regulatory
subunits
Subunits break apart
and catalytic subunits
phosphorylate target
proteins.

Inositol-Lipid (IP3-DAG)
Pathway

(+) phorbol
esters

Hormone Action
peptide and cathecolamines
R

TSH

TSH

TSH R
protein

I
I

T-4

2nd
messenger

I
effect
I

Hormone Action
Steroid, Thyroid
T-3
TBG

T-3
T-3

T-3 R
T-3 R

Increased HR

receptors

Cellular responses to cAMP vary

among different cell types