Announcements

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Announcements

• Today
• Signaling pathways and 2nd messengers
• Pituitary gland
• Course evaluations

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Two types of hormones

• Lipid Soluble
• Steroid hormones (estrogen, testosterone)
• Thyroid hormones
• Lipid Insoluble
• Peptides and Proteins (insulin)
• Catecholamines (adrenalin)

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Two types of hormones

1. Lipid-soluble

Carrier molecule
Hormone molecule
Cytoplasmic receptor
Nuclear receptor
Transcription Translation long lasting effects
Nucleus
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Two types of hormones

1. Lipid-insoluble

Hormone molecule
Plasma membrane receptor
Second Messenger
Effector Protein
Cellular effects
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Signal Transduction
Signal
Reception, Transduction
Amplification
Second Messengers
Regulators
Specific Effectors
Cellular Response
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Types of Second Messengers

• Cyclic nucleotides
• cAMP, cGMP
• Inositol phospholipid
• Inositol 1,4,5 triphosphate (IP3)
• 1,2-diacylglycerol (DAG)
• Calcium ions (Ca)

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cAMP / Protein Kinase A Pathway
Ri
Rs
Adenylate Cyclase
Gs
Gi
inhibits
stimulates
ATP
cAMP
Protein Kinase A
Ion Channels
Membrane Pumps
Metabolic Enzymes
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cAMP / Protein Kinase A Pathway
Ri
Rs
Adenylate Cyclase
Gs
Gi
ATP
cAMP
Regulatory subunit
Protein Kinase A
Catalytic subunit
Effects
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Inositol Phospholipid Pathway
Phospholipase C
PIP2
DAG
PS
Protein Kinase C
G-protein
IP3
Ca
Cellular Response
Intracellular Ca stores
Other Ca Dependent processes
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1. Receptor / G-protein activate phospholipase C
2. PLC catalyzes PIP2 ? IP3 and DAG
3. IP3 ? release of Ca from intracellular stores
   (ER)
4. DAG (together with Ca and PS) activate Protein
   Kinase C

Phosphatidylserine
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Calcium as second messenger
Ca
Guanylate kinase
GTP
cGMP
Protein Kinase G
Neurotransmitter release Muscle contraction
Ca
Calcium / Calmodulin
Intracellular Ca stores
Protein Kinase C
Adenylate cyclase
Metabolic Enzymes
Cam Kinase II
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Pituitary gland

• Master gland
• Secretes 9 hormones that control other glands
• 2 distinct parts
• Anterior pituitary (adenohypophysis)
• Posterior pituitary (neurohypophysis)
• Both parts controlled by neurosecretory cells of
  the hypothalamus (part of the brain!)

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Neural Inputs
Hypothalamus
Portal Blood Vessels
Fig 9-15
Anterior Pituitary -glandular tissue
Posterior Pituitary
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Anterior Pituitary
Hypothalamus
Hormone 1
Portal blood vessels
Hormone 1
Anterior Pituitary
Target Tissue
Hormone 2
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Posterior Pituitary
Hypothalamus
Hormone 1
Portal blood vessels
Posterior Pituitary
Target Tissue
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• Neurosecretory neurons ? Anterior Pituitary
• Secrete hormones into portal blood vessels
• Regulate secretion of other hormones from
  anterior pituitary
• Neurosecretory neurons ? Posterior Pituitary
• Secrete hormones directly into capillaries

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Anterior Pituitary

• 2 hormone system
• 1st hormone stimulates or inhibits release of
  other hormones from anterior pituitary
• 2nd hormone has effect on target tissue

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Examples

• 1st hormone
• Corticotropin-releasing hormone (CRH)
• Thyroid hormone releasing hormone (TRH)
• Prolactin-inhibiting hormone (PIH)

• 2nd hormone
• Adrenocorticotropin hormone (ACTH)
• Thyroid stimulating hormone (TSH)
• Prolactin

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Control of Anterior Pituitary
Hypothalmic Neurosecretory cells
Negative feedback
Releasing and release-inhibiting hormones
Anterior pituitary gland
ACTH Thyroid Stimulating Hormone
Growth hormone
Other Endocrine Tissue
Non-endocrine Tissue
Metabolic response
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Posterior Pituitary

• Neurosecretory cells secrete hormones directly
  onto capillaries
• Only 2 hormones
• Antidiuretic hormone (ADH, also called
  vasopressin)
• Water retention by the kidney
• Oxytocin
• Uterine contractions during childbirth
• Milk ejection during breast feeding

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The Adrenal Glands

• An example of Pituitary control over other
  endocrine tissue
• One gland attached to the top of each kidney

Adrenal Medulla
Adrenal Cortex
Fig 9-32
Kidney
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• Adrenal Cortex
• Steroid hormones
• Aldosterone
• Cortisol
• Small amounts of testosterone, progesterone

• Adrenal Medulla
• Catecholamine
• Epinipherine (adrenalin)
• Norepinipherine (noradrenalin)

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Control of Adrenal Cortex
Stress, circadian rhythm and other neural input
Hypothalamic neurons
Corticotropin releasing hormone (CRH)
Anterior Pituitary
Adrenocorticotropic hormone (ACTH)
Adrenal cortex
Release of steroid hormones
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Adrenal Cortical Steroids

• Mineralocorticoids
• eg. aldosterone
• Controls ion transport in the kidney function
• Regulates expression of a Na channel
• Important for water reabsorption

• Glucocorticoids
• eg. cortisol
• Important for metabolism esp. glucose
• Activate enzymes (in liver) that increase glucose
  production
• ? blood glucose

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Adrenal Medulla

• Catecholamines stored in large vesicles within
  chromaffin cells of the adrenal medulla
• Chromaffin cells innervated by neurons of the
  sympathetic nervous system
• Fight or flight response

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Sympathetic nerve terminal
Acetycholine synapse
Ca
Adrenal medulla
Catecholamine containing vesicles
Chromaffin cell
Blood vessel
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• Ach depolarizes chromaffin cell by activating
  nicotinic Ach receptors
• Opens voltage-gated Ca channels
• Ca causes fusion of vesicles
• Release of catecholamine into blood stream

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• Catecholamines released by adrenal medulla
• epinipherine 80
• norepiniphrine 20
• Also neurotransmitter
• Norepinephrine primary SNS

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Effects of catecholamines depend upon receptor
type

• Activate adrenoreceptors
• Two types ? and ?

?1
?2
?2
?1
Adenylate cyclase
Phospholipase C
cAMP
IP3 DAG
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Potential effects of catecholamine receptor
activation

• Heart
• ?,? mediated ? - contraction, HR
• Smooth Muscle (Blood vessels and lungs)
• ? contraction
• ? relaxation
• Metabolism
• ? - ? glycogenolysis ? glucose
• Neural
• ? - ? K channel conductance

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Some clinical stuff

• ? adrenoreceptor agonists used to treat asthma
• ? blockers used to treat high blood pressure

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Summary

• Pituitary gland
• Hypothalamic control
• Anterior 2 hormone system
• Posterior direct hormone release into blood
  stream
• Adrenal gland
• Cortex steroid hormones
• Medulla - catecholamines

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Blood Glucose Regulation

• Endocrine pancreas
• Only 2 of entire pancreas,
• the rest produces digestive enzymes (exocrine)
• Islets of Langerhans
• Insulin (? cells)
• Glucagon (? cells)
• Somatostatin (? cells)

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• Diabetes
• 2 million Canadians
• 9 billion per year health care costs
• Insulin isolated by Banting Best 1922, U of T
  Dept of Physiology (1923 Nobel Prize)
• Type 1
• No or very little insulin produced
• Type 2
• Reduced cellular response to insulin
• Consequences
• Death
• Blindness
• Kidney disease
• Limb amputation

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Hormonal control of blood glucose
In the GI tract, 80 of all carbohydrate is
digested to glucose
Basically
Glycogen

• Glucose

Used for glucose storage
Used for ATP production
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Insulin

• Stimulus for secretion is high blood glucose
• Secreted by ? cells
• Leads to glucose uptake and storage in liver,
  muscle and fat tissue.
• Effect is to ? blood glucose
• Danger of Diabetes is hyperglycemia

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Insulin Effects on Muscle and Fat Tissue

• Insulin initiates transfer of glucose
  transporters to cell membrane
• ? blood glucose
• ? production of glycogen

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Effects in Muscle Fat
Glycogen synthesis
glucose
storage vesicle
SNARE dependent transport
Insulin
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In the Liver

• insulin stimulates the synthesis of an enzyme
  (glucokinase)
• Required to trap glucose in the cell
• initiates glycogen production

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Effects in Liver
GLUT2
Glycogen synthesis
X
glucose
Glucose 6-phosphate
glucose
glucokinase
trapped
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Other hormones

• Glucagon
• Secretion stimulated by low blood glucose
• Activates enzymes for gluconeogenesis and
  glycogenolysis
• Leads to ? blood glucose levels
• Somatostatin
• Regulates secretion of insulin and glucagon

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Glucose Regulation Summary

• Endocrine pancreas
• Secretion of several hormones important for blood
  glucose regulation
• Insulin ? glucose uptake and storage
• Different effects on liver and muscle fat
• Glucagon ? glucose production

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• Today
• Finish blood glucose
• Some words about the final
• Sample questions

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Effects in Muscle Fat
GLUT4
Glycogen synthesis
glucose
storage vesicle
SNARE dependent transport
Insulin
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Insulin Effects on Muscle and Fat Tissue

• Insulin initiates transfer of glucose
  transporters to cell membrane
• ? blood glucose
• ? production of glycogen

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In the Liver

• insulin stimulates the synthesis of an enzyme
  (glucokinase)
• Required to trap glucose in the cell
• initiates glycogen production

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Effects in Liver
GLUT2
Glycogen synthesis
X
glucose
Glucose 6-phosphate
glucose
glucokinase
trapped
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Other hormones

• Glucagon
• Secretion stimulated by low blood glucose
• Activates enzymes for gluconeogenesis and
  glycogenolysis
• Leads to ? blood glucose levels
• Somatostatin
• Regulates secretion of insulin and glucagon

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Glucose Regulation Summary

• Endocrine pancreas cell type
• Secretion of several hormones important for blood
  glucose regulation
• Insulin ? glucose uptake and storage
• Different effects on liver and muscle fat
• Glucagon ? glucose production