Download Hormones that bind to intracellular receptors

Basic Biochemistry
CLS 233
1st semester, 2015
Ch:6
Hormones
-Classification
- Mechanism of action
- Effect on the regulation of cellular metabolic activity
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Important Definitions
• What are hormones?
Hormones are organic chemical messengers produced and
secreted by endocrine cells into the bloodstream.
Hormones regulate, and control a wide range of physiologic
functions.
2
Important Definitions
• What are target cells?
Target cells refer to cells that contain specific receptors (binding
sites) for a particular hormone.
Once a hormone binds to receptors on a target cell, it will initiate a
signal transduction pathway leading to responses in the cytoplasm,
enzyme activation, or a change in gene expression
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Important Definitions
What are hormone receptors?
They are binding sites on the target cell
(either on the surface or in the cytoplasm
or nucleus of the target cell) that are
activated only when specific hormones bind
to them.
If a hormone does not/cannot bind to it’s
receptor, then no physiologic effect results.
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HORMONES CAN BE CLASSIFIED
IN SEVERAL WAYS
Hormones can be classified according to:
- chemical composition
- solubility properties
- location of receptors
- the nature of the signal used to mediate hormonal action within the
cell.
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Classification depending on chemical composition
Polypeptides
Insulin
Glucagon
Somatotropin
Vasopressin
Oxytocin
Thyrotropin
Steroids
Estrogen
Testosterone
Aldosterone
Corticosterone
Progesterone
Cortisol
Amino acid
Epinephrine
Norepinephrine
Dopamine
Melatonin
Serotonin
Thyroxine
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Steroid Hormones
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Classification of hormones by
mechanism of action.
I. Hormones that bind to intracellular receptors
II. Hormones that bind to cell surface receptors
A. The second messenger is cAMP
B. The second messenger is cGMP
C. The second messenger is calcium or phosphatidylinositols
(or both)
D. The second messenger is a kinase or phosphatase cascade
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I- Hormones that bind to intracellular receptors
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II. Hormones that bind to cell surface receptors
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Notes
The hormones in group I are lipophilic.
The ligand-receptor complex is assumed to be
the intracellular messenger in this group.
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Notes
Group II hormones have membrane receptors & use
intracellular messengers
They are Water -soluble, have no transport proteins
(and therefore have a short plasma half-life), and
initiate a response by binding to a receptor located in
the plasma membrane.
They generate intracellular signals, which include:
cAMP, cGMP, Ca2+, phosphatidylinositides.
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General features of hormone classes
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SOME HORMONES HAVE PLASMA
TRANSPORT PROTEINS
Steroids and thyroid (class I) hormones, have specialized plasma
transport proteins.
Hormones, when bound to the transport proteins, cannot be
metabolized, thereby prolonging their plasma half-life (t1/2).
The hydrophilic hormones—generally class II and of peptide
structure—are freely soluble in plasma and do not require
transport proteins.
Hormones such as insulin, growth hormone, ACTH, and TSH circulate
in the free, active form and have very short plasma half lives.
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What is a half-life (t1/2) ?
•
•
Hormones are broken down (metabolized) and/or excreted from the
body.
The rate of removal from the circulation is fairly constant for a
given hormone.
The length of time it takes to remove half of the amount of hormone
from the circulation is the half-life of that hormone.
Amount of Hormone
•
100%
50%
0%
Time
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SIGNAL GENERATION
The Ligand-Receptor Complex Is the Signal for Group I Hormones
The lipophilic group I hormones diffuse through the plasma membrane
of all cells but only encounter their specific, high-affinity
intracellular receptors in target cells.
These receptors can be located in the cytoplasm or in the nucleus of
target cells.
The hormone-receptor complex first undergoes an activation reaction.
This receptor also contains nuclear localization sequences that assist in
the translocation from cytoplasm to nucleus.
The activated receptor moves into the nucleus, and binds with high
affinity to a specific DNA sequence called the hormone response
element (HRE).
By selectively affecting gene transcription and the consequent
production of appropriate target mRNAs, the amounts of specific
proteins are changed and metabolic processes are influenced.
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Mechanism of Action… [Group 2]
(-)
Liver
(+)
Phosphorylase
kinase (inactive)
Phosphoprotein
phosphatase
Adenylate
cyclase
Protein kinase
(Inactive)
Muscles
(+)
Protein kinase
(Active)
(+)
Glycogen
synthase a
(+)
Phosphorylase
kinase (active)
(+)
(+)
Glycogen
Glycogen
Phosphorylase b
Phosphorylase a
Glycogen
synthase b
Phosphoprotein
phosphatase
Glycogen
(+)
Insulin
Glucose-1-PO4
GLYCOGENOLYSIS
Hormone Action using cAMP Second Messenger
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Hormone Metabolism
Hormones That Affect
Fuel metabolism







Insulin
Glucagon
Somatostatin
Catecholamines
Steroid Hormones
Thyroid Hormones
Growth Hormones
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Hormone Metabolism
Effect of hormones on the regulation of cellular
metabolic activity
Pathways
Insulin
Glucagon
Epi
T3, T4
Cortisol
GH
Glycolysis
(+)
(-)
(+)
(+)
(-)
(-)
Glycogenesis
(+)
(-)
(-)
(-)
(+)
(+)
Glycogenolysis
(-)
(+)
“Liver”
(+)
“L & M”
(+)
(-)
(+)
Gluconeogenesis
(-)
(+)
(+)
(+)
(+)
(+)
Lipogenesis
(+)
(-)
(-)
(-)
(+)
(-)
Lipolysis
(-)
(+)
(+)
(+)
(+)
(+)
Protein Synthesis
(+)
(-)
(-)
(+)
(+)
(++)
(+) Stimulated; (-) Inhibited
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