Download Lect 6 hormones 2

What are the effects of cortisol?
Finish Adrenal glands
cortisol
Adrenal medulla & catecholamines
Thyroid Gland
• Thyroid Hormones
• Calcium regulation
1. Energy Mobilization:
a. ↑ glucose production by liver
b. ↑ protein breakdown in muscle
c. ↑ fatty acids in blood
2. Permissiveness
a. Most other hormones work better in the
presence of cortisol
3. Anti-inflammatory
Adrenal Gland Part 2
Adrenal Medulla
Hormone
Zona
glomerulosa
• Recall cortisol is a lipid-soluble hormone
aldosterone
– Nuclear receptor activates transcription
Cortex
– e.g. cortisol ↑ tyrosine aminotransferase
transcription, an enzyme important for
glucose production in the liver
Zona
fasciculata
Cortisol and
Testosterone, progesterone
Zona
reticularis
Medulla
Epinephrine &
norepinephrine
Cortex
Medulla
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Adrenal Gland Part 2
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
Sympathetic nerve terminal
Acetycholine synapse
Ca++
Adrenal medulla
Catecholamine
containing vesicles
Chromaffin cell
Blood vessel
• 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
Epi
NE
• Catecholamines released by adrenal
medulla:
– 80% epinipherine
– 20% norepiniphrine
Recall Norepinephrine is the Sympathetic NS
postganglionic neurotransmitter
2
Effects of catecholamines depend
upon receptor type
• Activate adrenergic receptors
Overall, Epi or NE from adrenal
medulla have similar effects as NE
from SNS activity
– Two types: α and β
•
α2
α1
activates
β1
β2
Phospholipase C
Adenylate cyclase
IP3 & DAG
cAMP
•
•
Effects Epi/NE from adrenal medulla last 5-10X longer
than effects of SNS due to blood circulation
Epi is a little more effective at activating β receptors
than norepi
Epi is more effective at ↑ metabolic rate of all cells
inhibits
Summary
Thyroid
• 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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Thyroid
• Thyroid Hormones
– Produced in the follicle cells of the thyroid
– T3 triiodothyronine
– T4 thyroxine
Follicular Cells
• Both require iodine to be produced
• Thyroid hormones increase metabolic rate
in muscle, heart, liver and kidney
– Produce heat
Thyroid Follicle
Follicle Cell
Thyroid Follicle
Thyroid hormone chemistry
30-fold concentration of iodide
Iblood
Thyroid
peroxidase
II-
Na+
Na+
K+
T3
Formation and secretion
of thyroglobulin in vesicles
+ tyrosine
Thyroid
peroxidase
Monoiodotyrosine + I-
diiodotyrosine
Thyroglobulin + iodide
monoiodotyrosine + diiodotyrosine = 3,5,3 triiodotyrosine (T3)
endocytosis
Thyroglobulin + T3 and T4
diiodotyrosine + diiodotyrosine = thyroxine (T4)
proteolysis of thyroglobulin
Release of T3 and T4
T4
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What does TSH do
on the follicle cell?
Control of Thyroid
Cold
If –’ve feedback lost
Too much TSH
Get goiter
Hypothalamic neurons
TSH
Rs
Adenylate
Cyclase
Gs
Thyroid releasing hormone (TRH)
stimulates
ATP
Anterior Pituitary
cAMP
Thyroid Stimulating Hormone (TSH)
Protein Kinase A
Thyroid
Actions of thyroid hormone
T3, T4 lipid soluble → nuclear receptor
T3 is 3X more active than T4
In target tissues T4 → T3
TH has many effects on just about all tissues
Likely, 100s of enzymes ↑↑ in response to TH
Some TH responsive genes include:
• Glucose transporters (glut1)
• Na+,K+ ATPase
Increased breakdown
of thyroglobulin
Increased activity
of iodide pump
Increased rate of
Tyrosine iodination
Actions of thyroid hormone
1. ↑ In metabolic rate
Basal Metabolic rate
Release of thyroid hormones – T3 and T4
Thyroid hormone μg/day
2. ↑ responsiveness of β
adrenergic receptors (esp. heart and
nervous system) → excess thyroid hormone
resembles excess sympathetic nervous
system activity
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Actions of thyroid hormone
Growth & Development
• General growth rate
• Specific effects on nervous system, esp
myelin production
• Lack of iodine during development
→Stunted growth, called cretinism
Control of extracellular Calcium
Tissues
1. Bone
– 99% of total body calcium
– Osteoblasts produce bone
– Osteoclasts resorb bone
Clinical
→Enlargement of the thyroid, called goiter
→Due to lack of thyroid hormones and
overstimulation of the thyroid gland by
TSH
→Because no negative feedback
Control of extracellular Calcium
•
Hormonal Control
1. Parathyroid hormone (PTH)
2. Calcitriol (1,25 dihydroxyvitamin D)
3. Calcitonin
2. Kidney
– Excretion of calcium
3. GI tract
– Calcium absorption
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How do parathyroid cells sense
calcium?
Parathyroid
• Low blood Ca++
stimulates release of
parathyroid hormones
• Act to increase blood
Ca++ by
– ↑ Ca++ release from bone
– ↑ Ca++ absorption in gut
– ↑ Ca++ reabsorption in
kidney
• Calcium-sensing receptor
– Parathyroid cells
– G-protein coupled receptor couple to IP3 pathway
• This is odd, because in almost all other
cells, ↑ [Ca++] causes ↑ secretion,
Ca++
--
Phospholipase C
• In parathyroid cells,
↑ [Ca++] causes ↓ secretion
IP3
???
Ca++
PTH
Intracellular Ca++
stores
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Vitamin D
Skin
Diet
7-dehydrocholesterol
sunlight
1,25-OH Vitamin D acts as a co-factor to ↑
transcription of a Ca++ channel in the
intestinal epithelium
Vitamin D3
Plasma Vitamin D
Vitamin D
Liver
25-OH Vitamin D
GI tract
1,25-OH2 Vitamin D
Ca++
Kidney
25-OH Vitamin D
Parathyroid Hormone
1,25-OH2 Vitamin D
transcription
Ca++
Na+
Intestinal epithelial cell
Plasma 1,25-OH2 Vitamin D
Calcitonin
• Produced in parafollicle cells of the thyroid
gland (C-cells)
• High Blood Ca++ stimulates release of
calcitonin (also by a calcium-sensing
receptor)
• Act to decrease blood Ca++ by
High Ca++
Calcitonin
Mobilize Ca
From Bone
Low blood Ca++
↑ Parathyroid hormone
Reabsorb Ca
In the kidney
– ↓ Ca++ release from bone
– ↓ Ca++ reabsorption in kidney
↑1,25 OH2 Vit D
from kidney
Increase absorption
of Ca++ from intestine
restore blood Ca++
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