Hormones
Hormones
• Robert Wadlow
– 8’-11” tall
– 496 pounds
– Size 37 shoe
• Too much growth
hormone
Topics:
• Types of hormones
• Signal transduction pathways
• Major Hormone systems
• Hormonal control of physiological
processes
Hormones
Mechanisms of Secretion
Ca++
•
Another form of communication
•
Types of Secretion
1.
2.
3.
4.
Autocrine – affects the secreting cell
Paracrine – affects neighbouring cell
Endocrine – secreted into bloodstream
Exocrine – secreted onto body surface,
including surface of gut
Neuron
Ca++
Neurosecretory cell
Ca++
Capillary
Simple Endocrine Cell
Ca++
Intracellular Ca stores
1
• Secretory Pathway in Endocrine cells
Exocytosis
• Neurosecretory cells
Like synaptic vesicle
secretion, these
steps also require
SNARE proteins
Ca++
– Work like all neurons
Secretory vesicle
Sensory Input → APs → secretion
– Except secrete into bloodstream
Golgi
Nucleus
Rough ER
Two types of hormones
Two types of hormones
1. Lipid-soluble
Carrier molecule
• Lipid Soluble
Hormone molecule
– Steroid hormones (eg cortisol, estrogen, testosterone)
– Thyroid hormones
• Lipid Insoluble
– Peptides and Proteins (eg insulin, ACTH)
– Catecholamines (eg adrenalin)
Cytoplasmic receptor
Nuclear receptor
Transcription &
Translation
long lasting effects
Nucleus
2
Two types of hormones
Signal Transduction
Signal
2. Lipid-insoluble
Hormone molecule
Reception, Transduction
Plasma membrane receptor
Amplification
Second Messenger
Second Messengers
Regulators
Specific Effectors
Effector Protein
Cellular effects
1 molecule
Cellular Response
Types of Second Messengers
• Cyclic nucleotides
– cAMP, cGMP
• Inositol phospholipid
– Inositol 1,4,5 triphosphate (IP3)
– 1,2-diacylglycerol (DAG)
• Calcium ions (Ca++)
10,000 molecules
3
cAMP / Protein Kinase A Pathway
Ri
Rs
Adenylate
Cyclase
Gs
Gi
stimulates
cAMP / Protein Kinase A Pathway
Ri
Rs
inhibits
ATP
Adenylate
Cyclase
Gs
ATP
cAMP
Protein Kinase A
Gi
cAMP
Regulatory subunit
Protein Kinase A
Catalytic subunit
Ion
Channels
Membrane
Pumps
Metabolic
Enzymes
Effects
Inositol Phospholipid Pathway
Phospholipase C
PIP2
DAG
Phosphatidylserine
Protein Kinase C
G-protein
IP3
Ca++
Cellular Response
Intracellular Ca++
stores
Other Ca++
Dependent processes
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
4
Calcium as second messenger
Pituitary gland
• Master gland
Ca++
Guanylate kinase
– Secretes 9 hormones that control other
glands
• 2 distinct parts
GTP
cGMP
Protein Kinase G
Ca++
Intracellular Ca++
stores
Protein Kinase C
Cam Kinase II
• Both parts controlled by neurosecretory
cells of the hypothalamus (part of the
brain!)
Calcium / Calmodulin
Adenylate
cyclase
– Anterior pituitary (adenohypophysis)
– Posterior pituitary (neurohypophysis)
Metabolic
Enzymes
Anterior Pituitary
Hypothalamus
Pituitary
Hormone 1
Neurosecretory
neurons
Hypothalamal-Pituitary
Portal blood vessels
Hormone 1
Anterior Pituitary
Anterior Pituitary
Target Tissue
Anterior Pituitary endocrine cells
Hormone 2
5
Posterior Pituitary
Hypothalamus
• Neurosecretory neurons → Anterior Pituitary
Hormone 1
Portal blood vessels
Target Tissue
Posterior Pituitary
Anterior Pituitary
• 2 hormone system
• 1st hormone stimulates or inhibits release
of other hormones from anterior pituitary
• 2nd hormone has effect on target tissue
– Secrete hormones onto median eminence and
transported to Ant Pit by portal vessels
– Regulate secretion of other hormones from anterior
pituitary
• Neurosecretory neurons → Posterior Pituitary
– Secrete hormones directly into capillaries
1st hormone
– GnRH – Gonadotropin releasing
hormone
– GHRH - Growth Hormone
Releasing Hormone
– SS - Somatostatin
– Thyroid hormone releasing
hormone (TRH)
– Corticotropin-releasing hormone
(CRH)
– Prolactin-inhibiting hormone
(PIH)
2nd hormone
– FSH/LH – Follicle
Stimulating Hormone / LH
Luteinizing Hormone
– GH – Growth Hormone
– TSH - Thyroid stimulating
hormone
– ACTH -Adrenocorticotropin
hormone
– Prolactin
6
Control of Anterior Pituitary
Hypothalamus
GnRh
GHRH
SS
TRH
PIH
CRH
Hypothalmic Neurosecretory cells
Negative feedback
Releasing and release-inhibiting hormones
Anterior Pituitary
FSH &
LH
Growth
Hormone
TSH
Prolactin
ACTH
Anterior pituitary gland
Gonads
Many tissues
Thyroid Breasts
Growth hormone
prolactin
Adrenal Cortex
Germ cell development
Secrete Hormones
•Estrogen, Progesterone
•Testosterone
Protein synthesis
Metabolism
Secrete thyroid
hormones
Development &
Milk production
Secrete Cortisol
(aldosterone)
Non-endocrine Tissue
Metabolic response
Inhibits secretion
•
Neurosecretory cells secrete hormones
directly onto capillaries
Only 2 hormones:
1. Antidiuretic hormone (ADH, also called
vasopressin)
•
hormone
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
Water retention by the kidney
2. Oxytocin
•
•
Endocrine Tissue
stimulates secretion
Posterior Pituitary
•
ACTH
TSH
FSH / LH
Uterine contractions during childbirth
Milk ejection during breast feeding
Fig 9-32
Kidney
7
Functional Anatomy of Adrenal Glands
Hormone
Zona
glomerulosa
Cortex
Zona
fasciculata
aldosterone
Adrenal Cortex
• Steroid hormones
Cortisol and
Testosterone, progesterone
Zona
reticularis
Medulla
– Aldosterone
– Cortisol
– Small amounts of
testosterone,
progesterone
Adrenal Medulla
• Catecholamine
– Epinipherine (adrenalin)
– Norepinipherine
(noradrenalin)
Epinephrine &
norepinephrine
Cortex
Medulla
Adrenal Cortical Steroids
• Mineralocorticoids
– eg. aldosterone
– Controls ion transport
in the kidney function
– Regulates expression
of a Na channel
– Important for water
reabsorption
Control of Adrenal Cortex
Stress, circadian rhythm
and other neural input
• Glucocorticoids
– eg. cortisol
– Important for
metabolism esp. glucose
– Activate enzymes (in
liver) that increase
glucose production
– ↑ blood glucose
Hypothalamic neurons
Corticotropin releasing hormone (CRH)
Anterior Pituitary
Adrenocorticotropic hormone (ACTH)
Adrenal cortex
Release of steroid hormones
8
What is the effect of ACTH on the
adrenal cortical cells?
• Leads to the production and secretion of
depolarization
cortisol…..but how?
Rs
Adenylate
Cyclase
Gs
Ca++
cAMP
Protein Kinase A
1
1. Energy Mobilization:
a. ↑ glucose production by liver
b. ↑ protein breakdown in muscle
c. ↑ fatty acids in blood
2. Permissiveness
K+ channel
ATP
What are the effects of cortisol?
2
Activate enzymes
Req’d for cortisol production
a. Most other hormones work better in the
presence of cortisol
3. Anti-inflammatory
↑ cortisol
Adrenal Gland Part 2
Adrenal Medulla
Hormone
Zona
glomerulosa
• Recall cortisol is a lipid-soluble hormone
– Nuclear receptor activates transcription
– e.g. ↑ tyrosine aminotransferase transcription,
an enzyme important for glucose production
in the liver
Cortex
Zona
fasciculata
aldosterone
Cortisol and
Testosterone, progesterone
Zona
reticularis
Medulla
Epinephrine &
norepinephrine
Cortex
Medulla
9
Adrenal Gland Part 2
Adrenal Medulla
Sympathetic nerve terminal
• 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
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
• Catecholamines released by adrenal
medulla:
– 80% epinipherine
– 20% norepiniphrine
Recall Norepinephrine is the Sympathetic NS
postganglionic neurotransmitter
10
Effects of catecholamines depend
upon receptor type
• Activate adrenoreceptors
– Two types: α and β
α1
Phospholipase C
IP3 & DAG
α2
β1
β2
Adenylate cyclase
cAMP
Potential effects of catecholamine
receptor activation
• Heart
– β mediated ↑ - contraction, HR
• Smooth Muscle
– α contraction (Blood vessels)
– β relaxation (lungs)
• Metabolism
– β - ↑ glycogenolysis → glucose
• Neural
– β - ↓ K+ channel conductance
Overall, Epi or Norepi from adrenal medulla
have similar effects as direct SNS activity
However:
1. Effects last 5-10X due to blood circulation from
adrenal medulla
2. Epi is more effective at activating β receptors
than norepi
3. Epi only causes weak constriction of blood
vessels of the muscles, compared to norepi
4. Epi is more effective at ↑ metabolic rate of all
cells
Summary
• Pituitary gland
– Hypothalamic control
– Anterior – 2 hormone system
– Posterior – direct hormone release into blood
stream
• Adrenal gland
– Cortex – steroid hormones
– Medulla - catecholamines
11