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Announcements

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Announcements Today Signaling pathways and 2nd messengers Pituitary gland Course evaluations – PowerPoint PPT presentation

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Title: Announcements


1
Announcements
  • Today
  • Signaling pathways and 2nd messengers
  • Pituitary gland
  • Course evaluations

2
Two types of hormones
  • Lipid Soluble
  • Steroid hormones (estrogen, testosterone)
  • Thyroid hormones
  • Lipid Insoluble
  • Peptides and Proteins (insulin)
  • Catecholamines (adrenalin)

3
Two types of hormones
  1. Lipid-soluble

Carrier molecule
Hormone molecule
Cytoplasmic receptor
Nuclear receptor
Transcription Translation long lasting effects
Nucleus
4
Two types of hormones
  1. Lipid-insoluble

Hormone molecule
Plasma membrane receptor
Second Messenger
Effector Protein
Cellular effects
5
Signal Transduction
Signal
Reception, Transduction
Amplification
Second Messengers
Regulators
Specific Effectors
Cellular Response
6
Types of Second Messengers
  • Cyclic nucleotides
  • cAMP, cGMP
  • Inositol phospholipid
  • Inositol 1,4,5 triphosphate (IP3)
  • 1,2-diacylglycerol (DAG)
  • Calcium ions (Ca)

7
cAMP / Protein Kinase A Pathway
Ri
Rs
Adenylate Cyclase
Gs
Gi
inhibits
stimulates
ATP
cAMP
Protein Kinase A
Ion Channels
Membrane Pumps
Metabolic Enzymes
8
cAMP / Protein Kinase A Pathway
Ri
Rs
Adenylate Cyclase
Gs
Gi
ATP
cAMP
Regulatory subunit
Protein Kinase A
Catalytic subunit
Effects
9
Inositol Phospholipid Pathway
Phospholipase C
PIP2
DAG
PS
Protein Kinase C
G-protein
IP3
Ca
Cellular Response
Intracellular Ca stores
Other Ca Dependent processes
10
  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
11
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
12
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!)

13
Neural Inputs
Hypothalamus
Portal Blood Vessels
Fig 9-15
Anterior Pituitary -glandular tissue
Posterior Pituitary
14
Anterior Pituitary
Hypothalamus
Hormone 1
Portal blood vessels
Hormone 1
Anterior Pituitary
Target Tissue
Hormone 2
15
Posterior Pituitary
Hypothalamus
Hormone 1
Portal blood vessels
Posterior Pituitary
Target Tissue
16
  • 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

17
Anterior Pituitary
  • 2 hormone system
  • 1st hormone stimulates or inhibits release of
    other hormones from anterior pituitary
  • 2nd hormone has effect on target tissue

18
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

19
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
20
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

21
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
22
  • Adrenal Cortex
  • Steroid hormones
  • Aldosterone
  • Cortisol
  • Small amounts of testosterone, progesterone
  • Adrenal Medulla
  • Catecholamine
  • Epinipherine (adrenalin)
  • Norepinipherine (noradrenalin)

23
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
24
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

25
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

26
Sympathetic nerve terminal
Acetycholine synapse
Ca
Adrenal medulla
Catecholamine containing vesicles
Chromaffin cell
Blood vessel
27
  • 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

28
  • Catecholamines released by adrenal medulla
  • epinipherine 80
  • norepiniphrine 20
  • Also neurotransmitter
  • Norepinephrine primary SNS

29
Effects of catecholamines depend upon receptor
type
  • Activate adrenoreceptors
  • Two types ? and ?

?1
?2
?2
?1
Adenylate cyclase
Phospholipase C
cAMP
IP3 DAG
30
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

31
Some clinical stuff
  • ? adrenoreceptor agonists used to treat asthma
  • ? blockers used to treat high blood pressure

32
Summary
  • Pituitary gland
  • Hypothalamic control
  • Anterior 2 hormone system
  • Posterior direct hormone release into blood
    stream
  • Adrenal gland
  • Cortex steroid hormones
  • Medulla - catecholamines

33
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)

34
  • 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

35
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
36
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

37
Insulin Effects on Muscle and Fat Tissue
  • Insulin initiates transfer of glucose
    transporters to cell membrane
  • ? blood glucose
  • ? production of glycogen

38
Effects in Muscle Fat
Glycogen synthesis
glucose
storage vesicle
SNARE dependent transport
Insulin
39
In the Liver
  • insulin stimulates the synthesis of an enzyme
    (glucokinase)
  • Required to trap glucose in the cell
  • initiates glycogen production

40
Effects in Liver
GLUT2
Glycogen synthesis
X
glucose
Glucose 6-phosphate
glucose
glucokinase
trapped
41
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

42
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

43
  • Today
  • Finish blood glucose
  • Some words about the final
  • Sample questions

44
Effects in Muscle Fat
GLUT4
Glycogen synthesis
glucose
storage vesicle
SNARE dependent transport
Insulin
45
Insulin Effects on Muscle and Fat Tissue
  • Insulin initiates transfer of glucose
    transporters to cell membrane
  • ? blood glucose
  • ? production of glycogen

46
In the Liver
  • insulin stimulates the synthesis of an enzyme
    (glucokinase)
  • Required to trap glucose in the cell
  • initiates glycogen production

47
Effects in Liver
GLUT2
Glycogen synthesis
X
glucose
Glucose 6-phosphate
glucose
glucokinase
trapped
48
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

49
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
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