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Transcript
Hormones in Animals
Endocrinology
D R Davies
School of Biological Sciences
Purves Life: the Science of Biology Chapters 41
(Animal Hormones) and 15 (Cell Signalling)
Lecture 13 Learning Outcomes
At the end of this lecture you should be able to:
• Describe the general properties of hormones,
with examples
• Know the location of the major endocrine glands
and the types of hormone secreted
• Outline the steps in the study of hormones
• Explain the different types of hormone receptor
and describe in outline the transduction
mechanism
Communication between cells in multicellular organisms
For a multicellular organism to survive it must be able
to respond to changes in the external and internal
environment - individual cells must be able to
communicate with one another communication
between cells occurs via 4 distinct mechanisms
 Cell-to-cell communication via gap junctions in the
plasma membrane
 Paracrine control via locally acting chemical signals
 Electrical signals via the nervous system
 By chemical signals (hormones) released into the
bloodstream
Definition of hormone
• A specific chemical substance formed in
one organ (endocrine gland) and transported
in the bloodstream to another organ (Target
Organ)where it affects the metabolism of
that organ.
• First coined in 1902 by Bayliss and Starling
who were the first to show the existence of
the hormone - secretin.
Definition of hormone (2)
• Hormones are information transferring
molecules which move from one cell to
another for the benefit of the organism as a
whole Huxley)
Endocrine
Cell
Target Cell
H
Physiological effects of
hormones are proportional to
hormone concentration
• Hormones are only
effective over a narrow
concentration range
• The EC50 value is the
hormone concentration
required to produce
50% of the maximal
response
100%
50%
Hormones:
• do not initiate reactions but rather they
effect the rate of pre-existing metabolic
functions in a positive or negative fashion
• some hormones have specific effects on a
single cell type, others a more general effect
• hormones are effective at minute
concentrations - range 10-12 to 10-8 M
• hormones have a very short half-life in
circulation ( ranging from minutes to hours)
Hormone concentration
• Hormones are inactivated or degraded to an
inactive form (H*)at a constant rate
• It follows that the level of hormone in
circulation is dependent on the rate of
secretion
Endocrine
Cell
Target Cell
[H]
H*
Physiological effects of
hormones are timed responses
Hormone Concentration
and Physiological Response
• The effects of
hormones occur in a
regulated and timed
manner
• Hormone levels
increase in response to
a physiological signal
which results in an
increased secretion of
hormone
Hormone
Physiol.
Response
Time
• hormone levels decrease
when secretion ceases
Endocrine Glands
What kinds of hormones
does each gland
produce?
Fig. 23-20
Hypothalamus: releasing peptide hormone acting on the
anterior pituitary : GHRH, CRH, TRH GnRH
Anterior Pituitary: Growth Hormone (GH), Corticotrophin
(ACTH), Thyroid Stimulating hormone (TSH), Luteinizing
hormone (LH), Follicle stimulating hormone (FSH)
Posterior Pituitary: oxytocin, vasopressin (ADH)
Pancreatic Islets of Langerhans: insulin and glucagon
Adrenal cortex: aldosterone and cortisol
Adrenal Medulla: Adrenaline and Noradrenaline
Thyroid Gland: thyroxine and Tri-iodothyronine
Testis: testosterone (androgen)
Ovary and placenta: oestradiol (oestrogens), progesterone
Hypothalamus and the
Pituitary Gland
Endocrine action coordinated
here. It makes sense: it’s
right next to your brain.
Fig. 23-22
Different types of hormones
Glycoprotein hormones e.g TSH, LH and FSH
Small peptide hormones : oxytocin, vaspressin (ADH) GnRH
Larger peptide hormones: insulin, ACTH
Catecholamine hormones: adrenaline and noradrenaline (a.k.a.
epinephrine and norepinephrine in the USA)
Thyroid hormone: thyroxine and triiodothyronine
Steroid hormones: cortisol, progesterone, testosterone, (o)estradiol
Fatty Acid -based hormones: prostaglandins
Peptide Hormones from the Posterior Pitutary
Insulin Structure
Steroid Hormones
•Lipid hormones
•Cross plasma
membranes
readily
•Interact with
intracellular
receptors
•Regulate gene
transcription
Adrenaline (epinephrine)
Epinephrine
OH
OH H H
HO
C C N CH3
H H
Methods of studying hormones and
their effects
Removal of the source of hormones:
If you remove the endocrine gland there is a measurable
physiological consequence:
• remove pancreas - causes diabetes mellitus (high blood
glucose)
• destroy b-cells in pancreas by injecting streptozotocin
- also results in diabetes
•castration - results in loss of secondary sexual
characteristics
Methods of studying hormones and
their effects
Make extracts of the removed tissue and administer the
the hormone deficient animal:
there is a measurable reversal physiological consequence:
• pancreatic extracts lower blood glucose) in
streptozotocin - induced in diabetes
• administration of testosterone restores secondary
sexual characteristics
•Proof that the endocrine gland secretes a chemical agent
with hormonal effects
Methods of studying hormones and
their effects
•Identify and characterise the hormone
•Make a synthetic version of the hormone and show that it
has similar effects
•Identify the target tissue (s)
•What are the metabolic and physiological effects of the
hormone?
•Make radiolabelled hormone (e.g. I125-insulin, 3Hoestradiol
•Hormone specfically retained in target tissue (by a high
affinity receptor)
•Examine properties of hormone receptor
•Purify and characterise receptor
•characterise the metabolic effects of hormone within
the target tissue
Hormones which bind to plasma membrane receptors:
• Hormones bind to specific receptors on the
outside of the plasma membrane of the cell and
exert rapid and specific effects on metabolism
and longer term effects gene transcription
G-protein linked receptors
e.g. adrenaline and glucagon receptors
Activated!
Second
Messenger
Effects
Activation of Insulin Receptor
Effects of Hormones
• In all cases activation of the receptor can lead to a cascade
of related and consequential molecular events inside the
cell.
• Events including generation of second messengers,
changes in ion fluxes, activation or inhibition of protein
kinases, activation or inhibition of transcription factors
• eventually lead to the regulation of the activity of key
metabolic enzymes or other cellular function or changes
in the level of transcription of genes coding for key
proteins
Intracellular Signalling Cascades
Signal Transfer
Signal
Transformed
and Relayed
Signal
Amplified
Signal Diverges
Modulated
Effect
Signalling via the insulin receptor
Mode of Action of Steroid and Thyroid Hormones
•
•
•
•
These hormones are produced continuously
They are not stored in the endocrine gland
The hormones cross cell membranes readily
Bind to receptors in the cytoplasm or nuclei
of target cells
• These steroid-receptor complexes act as
transcription factors regulating specific gene
expression
• The effects of steroid and thyroid hormones
usually take several hours to take effect
Activation of Protein Kinases