Download Hormone

Endocrine system
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Define Hormone

The term hormone is derived from a Greek verb meaning
– to excite or arouse

Hormone is a chemical messenger that is released in one
tissue (endocrine tissue/gland) and transported in the
bloodstream to reach specific cells in other tissues

Regulate the metabolic function of other cells

Have lag times ranging from seconds to hours

Tend to have prolonged effects

Hormone actions must be terminated – how?
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Endocrine versus Nervous system
• Both use chemical communication
• Both are being regulated primarily by negative feedback
Neurotransmitters
Hormones
 Released in synapse
• Released to bloodstream
 Close to target cells
• Can be distant from target
cells
 Signal to release by
action potential
 Short live effect
 Crisis management
• Different types of signal
• Long term effect
• Ongoing processes
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Control of Hormone Release
 Blood levels of hormones:
 Are controlled by negative feedback systems
 Vary only within a narrow desirable range
 Hormones are synthesized and released in response to:
 Humoral stimuli
 Neural stimuli
 Hormonal stimuli
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Humoral Stimuli
 Secretion of hormones in
direct response to changing
blood levels of ions and
nutrients
 Example: concentration
calcium ions in the blood
of
 Declining
blood
Ca2+
concentration stimulates the
parathyroid
glands
to
secrete PTH (parathyroid
hormone)
 PTH
causes
Ca2+
concentrations to rise and
the stimulus is removed
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Neural Stimuli
 Neural stimuli – nerve fibers
stimulate hormone release
 Preganglionic sympathetic
nervous system (SNS) fibers
stimulate the adrenal medulla
to secrete catecholamines
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Figure 16.5b
Hormonal Stimuli
 Hormonal stimuli – release of
hormones in response to
hormones produced by other
endocrine organs
 The hypothalamic hormones
stimulate
the
anterior
pituitary
 In turn, pituitary hormones
stimulate targets to secrete
still more hormones
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Classes of Hormones – by chemical structure
 Hormones can be divided into three groups
1. Amino acid derivatives
2. Peptide hormones
3. Lipid derivatives
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Chemical structure
AA derivatives
Tyrosine:
• Thyroid
hormones
• Catecholamines
(Epinephrine,
norepinephrine
Peptides
Tryptophan:
Dopamine,
serotonin,
melatonin
lipids
small proteins:
GH,PRL
Glycoproteins:
TSH, LH, FSH
Eicosanoid:
prostaglandins
short peptides:
ADH, OT
steroids
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A Structural Classification of Hormones
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Distribution of Hormones in bloodstream
 Hormones that are released into the blood are being
transported in one of 2 ways:
 Freely circulating
 Bound to transport protein
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Distribution of Hormones in bloodstream
 Freely circulating (most hormones)
 Hormones that are freely circulating remain functional for less
than one hour and some as little as 2 minutes
 Freely circulating hormones are inactivated when:
* bind to receptors on target cells
* being broken down by cells of the liver or kidneys
* being broken down by enzymes in the plasma or
interstitial fluid
 Bound to transport proteins – thyroid and steroid hormones
(>1% circulate freely)
 Remain in circulation longer
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Hormones: Classification
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Table 7-1
Receptors for hormones are located:
 on the cell membranes of target cells
 In the cytoplasm or nucleus
 Can you tell which hormone group/s will have
their receptors on the cell membrane and which
in the cytoplasm?
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Mechanisms of Hormone Action

Two mechanisms, depending on their chemical nature
1. Water-soluble hormones (all amino acid–based hormones
except thyroid hormone)
 Cannot enter the target cells
 Act on plasma membrane receptors
 Coupled by G proteins to intracellular second
messengers that mediate the target cell’s response
2. Lipid-soluble hormones (steroid and thyroid hormones)
 Act on intracellular receptors that directly activate
genes
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Indirect effect – through G-protein and 2nd messenger
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Receptors on the cell membrane
 Hormones do not induces changes in cell activity
directly but via the induction of the appearance and
action of other agents
 Hormones are referred to as first messengers and the
agents that are activated by the hormones are called
second messengers.
 All amino-acid hormones (with exception of the thyroid
hormone) exert their signals through a second messenger
system:
 cAMP
 PIP
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Amino Acid-Based Hormone Action: cAMP Second Messenger
 Hormone (first messenger) binds to its receptor, which
then binds to a G protein
 The G protein is then activated
 Activated G protein activates the effector enzyme
adenylate cyclase
 Adenylate cyclase generates cAMP (second messenger)
from ATP
 cAMP activates protein kinases, which then cause
cellular effects
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Hormone
Protein
receptor
G protein
(inactive)
G protein
activated
Effects on cAMP Levels
Many G proteins, once activated, exert their effects by changing the concentration
of cyclic-AMP, which acts as the second messenger within the cell.
Hormone
Hormone
Protein
receptor
Protein
receptor
G protein
activated
Acts as
second
messenger
Increased
production
of cAMP
adenylate
cyclase
G protein
activated
PDE
Enhanced
breakdown
of cAMP
kinase
Opens ion
channels
Activates
enzymes
If levels of cAMP increase,
enzymes may be activated
or ion channels may be
opened, accelerating the
metabolic activity of the cell.
Examples:
• Epinephrine and norepinephrine
(β receptors)
• Calcitonin
• Parathyroid hormone
• ADh, ACTH, FSH, LH, TSH
• Glucagon
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Reduced
enzyme
activity
In some instances, G protein
activation results in decreased
levels of cAMP in the
cytoplasm. This decrease has
an inhibitory effect on the cell.
Examples:
• Epinephrine and norepinephrine (α2 receptors)
1 Hormone (1st messenger)
binds receptor.
Adenylate cyclase
Extracellular fluid
G protein (GS)
5 cAMP acti-
vates protein
kinases.
Receptor
GDP
Hormones that
act via cAMP
mechanisms:
Epinephrine
ACTH
FSH
LH
Glucagon
PTH
TSH
Calcitonin
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2 Receptor
activates G
protein (GS).
3 G protein
activates
adenylate
cyclase.
4 Adenylate
cyclase
converts ATP
to cAMP (2nd
messenger).
Active
protein
kinase
Triggers responses of
target cell (activates
enzymes, stimulates
cellular secretion,
opens ion channel,
etc.)
Cytoplasm
Inactive
protein kinase
Figure 16.2, step 5
Amino Acid-Based Hormone Action: PIP-Calcium
 Hormone
G protein
binds
to
the
receptor
and
activates
 G protein binds and activates phospholipase
 Phospholipase splits the phospholipid PIP2 into
diacylglycerol (DAG) and IP3 (both act as second
messengers)
 DAG activates protein kinases; IP3 triggers release of
Ca2+ stores
 Ca2+ (third messenger) alters cellular responses
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Amino Acid-Based Hormone Action: PIP
Mechanism
Extracellular fluid
Hormone
DAG
1
4
2
Receptor
3
GTP
GTP
5
Gq
GTP
Catecholamines
TRH
ADH
GnRH
Oxytocin
GDP
IP3
Phospholipase C
Inactive
protein
kinase C
Triggers responses
of target cell
5
Endoplasmic
reticulum
Cytoplasm
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Active
protein
kinase C
PIP2
6
Ca2+
Ca2+- calmodulin
Figure 16.3
Hormone
Protein
receptor
G protein
(inactive)
G protein
activated
Effects on Ca2+ Levels
Some G proteins use Ca2+ as a
second messenger.
Hormone
Protein
receptor
G protein
activated
PLC,
DAG,
and IP3
Opening of
Ca2+ channels
Release of
stored Ca2+
from ER or SER
Ca2+ acts as
second messenger
Calmodulin
Activates
enzymes
Examples:
• Epinephrine and norepinephrine (α1 receptors)
• Oxytocin
• Regulatory hormones of hypothalamus
• Several eicosanoids
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Steroid Hormones: Action
Blood
vessel
Steroid
hormone
1 Most hydrophobic steroids are bound to
plasma protein carriers. Only unbound
hormones can diffuse into the target cell.
Cell surface receptor
2a
Rapid responses
1
2 Steroid hormone receptors are in the
cytoplasm or nucleus.
2
Protein
carrier
Nucleus
Cytoplasmic
receptor
Nuclear
receptor
2a Some steroid hormones also bind to
membrane receptors that use second
messenger systems to create rapid
cellular responses.
DNA
Interstitial
fluid
Cell
membrane
3
Endoplasmic
reticulum
5
New
proteins
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Transcription
produces mRNA
4
Translation
3 The receptor-hormone complex binds to
DNA and activates or represses one or
more genes.
4 Activated genes create new mRNA that
moves back to the cytoplasm.
5 Translation produces new proteins
for cell processes.
Figure 7-7, steps 1–5
Figure 18-4 Effects of Intracellular Hormone Binding
Steroid hormones diffuse through the plasma membrane
and bind to receptors in the cytoplasm or nucleus. The
complex then binds to DNA in the nucleus, activating
specific genes.
Diffusion through
membrane lipids
Thyroid hormones enter the cytoplasm and bind to
receptors in the nucleus to activate specific genes. They
also bind to receptors on mitochondria and accelerate
ATP production.
Transport across
plasma membrane
Target cell response
Target cell response
CYTOPLASM
Increased
ATP
production
Alteration of cellular
structure or activity
Alteration of cellular
structure or activity
Receptor
Translation and
protein synthesis
Translation and
protein synthesis
Receptor
Binding of receptors
at mitochondria and
nucleus
Binding of hormone
to cytoplasmic or
nuclear receptors
Transcription and
mRNA production
Transcription and
mRNA production
Receptor
Receptor
Gene activation
Gene activation
Nuclear
pore
Nuclear
envelope
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Binding of
hormone–receptor
complex to DNA
Binding of
hormone–receptor
complex to DNA
Location of
Receptor
Classes of
Hormones
Principle
Mechanism of Action
Cell surface
receptors (plasma
membrane)
Proteins and
peptides,
catecholamines
and eicosanoids
Generation of second
messengers which
alter the activity of
other molecules usually enzymes within the cell
Intracellular
receptors
(cytoplasm and/or
nucleus)
Alter transcriptional
Steroids and
activity of responsive
thyroid hormones
genes
http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/moaction/change.html
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How will we approach the endocrine system?
 We will group them according to their function in the
body:
 Hormones that control blood glucose levels
 Hormones that control minerals and water balance
 Hormones that are involved in growth and metabolism
 Hormones and the reproductive system
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Pancreas structure
 Exocrine pancreas (99% of volume)
 Cells (pancreatic acini) forming glands and
ducts that secrete pancreatic fluid and enzymes
with digestive function
 Endocrine pancreas (1%)
 Small groups of cells scattered in clusters
(pancreatic islets) that secrete hormones
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How does the body
control blood
glucose levels
Increased rate of
glucose transport into
target cell
Increased rate of
glucose utilization and
ATP generation
Falling blood glucose levels
Rising blood glucose levels
Increased conversion
of glucose to glycogen
Beta cells
secrete
insulin.
HOMEOSTASIS
DISTURBED
Increased amino acid
absorption and protein
synthesis
Increased triglyceride
synthesis in adipose
tissue
Blood glucose
levels decrease
Rising blood
glucose levels
HOMEOSTASIS
Normal blood
glucose levels
(70-110 mg/dL)
HOMEOSTASIS
DISTURBED
HOMEOSTASIS
RESTORED
Falling blood
glucose level
Alpha cells
secrete
glucagon
Blood glucose
levels increase
Increased breakdown of
glycogen to glucose (in
liver, skeletal muscle)
Increased breakdown
of fat to fatty acids (in
adipose tissue)
Increased synthesis
and release of glucose
(in liver)
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HOMEOSTASIS
RESTORED
Insulin
 A 51-amino-acid protein consisting of two amino acid chains
linked by disulfide bonds
 Insulin is released when glucose levels exceed normal levels (70110 mg/dl)
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http://www.chemistryexplained.com/images/chfa_02_img0437.jpg
Endocrine Reflex Pathways: Insulin release
KEY
Blood
glucose
Eat a meal
Stimulus
Stretch receptor
in digestive tract
Receptor
Efferent path
Effector
Afferent neuron
Tissue response
Sensory neuron
CNS
Negative feedback
Efferent neuron
Efferent neuron
Integrating center
Systemic response
Pancreas
Insulin
Blood
glucose
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Glucose uptake
and utilization
Target
tissues
Figure 7-9
Effects of Insulin Binding to its receptors
 Insulin facilitates entry of glucose cells by binding to a membrane
receptor
 The complex insulin-receptor make a specific carrier protein
(GLUT4) available
 Once at the cell surface, GLUT4 facilitates the passive
diffusion of circulating glucose down its concentration
gradient into cells.
 Receptors for insulin are present in most cell membranes (insulindependant cells)
 Cells that lack insulin receptors are cells in the brain, kidneys,
lining of the digestive tract and RBC (insulin-independent cells).
 Those cells can absorb and utilize glucose without insulin
stimulation.
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Effects of Insulin
 Acceleration of glucose uptake as a result from an increase of
the number of glucose carrier proteins
 Acceleration of glucose utilization and increased ATP
production
 Stimulation of glycogen formation in the liver and muscle cells
 Inhibits glycogenolysis (break down of glycogen) and
gluconeogenesis (glucose building)
 Stimulation of amino acid absorption and protein synthesis
 Stimulation of triglyceride formation in adipose tissue
 As a result glucose concentration in the blood decreases
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Glucagon
 Released by alpha cells
 A 29-amino-acid polypeptide hormone that is a potent
hyperglycemic agent (what does it mean?)
 it promotes:
 Glycogenolysis – the breakdown of glycogen to glucose
in the liver and skeletal muscle
 Gluconeogenesis – synthesis of glucose from lactic acid
and noncarbohydrates in the liver
 Release of glucose to the blood from liver cells
 breakdown of triglycerides in adipose tissue
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Other hormones that control glucose levels
 Glucocorticoids from the adrenal gland
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Adrenal (Suprarenal) Glands
 Structurally and functionally, they are two glands in one
 Adrenal medulla – neural tissue; part of the
sympathetic nervous system
 Adrenal cortex - three layers of glandular tissue that
synthesize and secrete corticosteroids
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Adrenal Cortex
 Synthesizes and releases steroid hormones called
corticosteroids
 Different corticosteroids are produced in each of the three
layers
 Zona glomerulosa – glomerulus- little ball. Secretes
mineralocorticoids – main one aldosterone
 Zona fasciculata – glucocorticoids (chiefly cortisol)
 Zona reticularis – gonadocorticoids (chiefly androgens)
 Check point - Which of the layers will be part of glucose
levels control?
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Zona fasciculata - Glucocorticoids (Cortisol/hydrocortisone)
 Main hormones secreted are the Cortisol/hydrocortisone and small
amounts of corticosterone
 It protects against hypoglycemia by stimulating catabolism of energy
stores.
 While adrenaline is responsible for rapid metabolic responses the
glucocorticoids are responsible for long-term stress:
 Glucocorticoids accelerate the rates of glucose synthesis and
glycogen formation – especially in the liver
 Adipose tissue responds by releasing fatty acids into the blood
and the tissues start to utilize fatty acids as source of energy glucose-sparing effect (GH has similar effect and will be
discussed later)
 Clucocorticoids also have anti-inflammatory effect – inhibit the
activities of WBC (use?)
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Blood Concentrations of Cortisol Vary Throughout
the Day
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Figure 23-4
Pathway For the Control of Cortisol Secretion
Circadian
rhythm
Stress
Hypothalamus
Anterior
pituitary
ACTH
Adrenal
cortex
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long-loop negative feedback
CRH
Cortisol
Immune
system
Liver
Muscle
Adipose
tissue
Function
suppressed
Gluconeogenesis
Protein
catabolism
Lipolysis
Figure 23-3
What happens when we can not control
glucose levels?
 What can be the reasons for the body’s inability to control
glucose levels?
 Why do you think it is dangerous to have high or low
blood glucose levels?
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Diabetes Mellitus (DM)
• Two types:
• Type I results from the destruction of beta cells and the
complete loss of insulin (hypoinsulinemia)
• Type II is the most common type (90%) and is a result of
decrease sensitivity of cells to insulin (insulin resistance).
Type II is accompanied by hyperinsulinemia (what is that?
Why?).
• Type II is associated with excess weight gain and obesity
but the mechanisms are unclear.
• Other reasons that were associated with type II diabetes:
pregnancy, polycystic ovary disease, mutations in insulin
receptors and others
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Type 1 and Type 2 Diabetes Mellitus
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Table 24.1
Diabetes Mellitus (DM) effects
 Increase in blood glucose due to diabetes causes
 Increase in glucose loss in urine
 Dehydration of cells – since glucose does not diffuse
through cell membrane and there is an increase in osmotic
pressure in the extracellualr fluid.
 In addition, the loss of glucose in the urine causes
osmotic diuresis - decrease in water reabsorption in the
kidney.
 The result is
 Polyuria – huge urine output and dehydration.
 Polydipsia – excessive thirst
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Diabetes Mellitus (DM) effects
 Polyphagia – excessive hunger and food consumption
because cells are starving
 Damage to blood vessels and poor blood supply to
different tissues
 Increase use of lipids as a source of energy by the cells
and increase release of keto bodies – ketosis and
changes of blood pH (acidosis). That leads to
increased respiratory rate
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http://www.medbio.info/Horn/Time%203-4/homeostasis_2.htm
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Hormones that control minerals and water
 We will see the different glands that control:
 Sodium – Adrenal gland
 Which layer and what hormone group?
 Calcium – Thyroid and parathyroid, kidney
 Water - hypothalamus
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Zona glomerulosa – Mineralocorticoids
 Aldosterone secretion is stimulated by:
 Rising blood levels of K+
 Low blood Na+
 Decreasing blood volume or pressure
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Zona glomerulosa - Mineralocorticoids
 The mineralocorticoids are steroids that affect the
electrolytes composition of the body extracellular fluids.
 Aldosterone – most important mineralocorticoid
 Maintains Na+ balance by reducing excretion of
sodium from the body
 Stimulates re-absorption of Na+ by the kidneys
 Prevents the loss of Na+ by the kidneys, sweat glands,
salivary glands and digestive system
 As a result of Na+ reabsorption there is also water
reabsorption
 The retention of Na+ is accompanied by a loss of K+
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What are the calcium functions in the body?
 Provides structure for bones and teeth
 Transmission of nerve impulses
 Assists in muscle contraction
 Part of blood clotting
 Regulates hormones and enzymes (2nd messanger)
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Protein hormones that control calcium
 Parathyroid gland – PTH
 PTH—most important hormone in Ca2+ homeostasis
 Thyroid gland – calcitonin
 Liver and Kidney - Calcitriol – also known as vitamin D3
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Calcium Balance in the Body
 Total body calcium = intake  output
 Total body calcium is divided into three pools
 Extracellular calcium (0.1% of total)
 Intracellular calcium (0.9% of total)
 Calcium in bone matrix (99% of total)
 Ca2+ ions in the extracellular fluid move freely in and out
of plasma
 Extracellular fluid calcium is carefully regulated
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Calcium Loss in Urine is Hormonally
Regulated
Small intestine
Dietary
calcium
Calcium
in feces
Ca2+
Calcitriol
(PTH, prolactin)
Bone
* Some calcium is secreted
into the small intestine.
ECF
Calcitonin
Ca2+
PTH
Calcitriol
Cortisol
[Ca2+]
2.5 mM
Electrochemical
gradient
Passive
filtration
Kidney
Ca2+ in
kidney
tubules
PTH
Calcitonin
Active
transport
[free Ca2+]
0.001 mM
Cells
Ca2+
in urine
KEY
PTH = parathyroid hormone
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Figure 23-17 (5 of 5)
Simple Endocrine Reflex: Parathyroid Hormone
Low plasma
[Ca2+]
Negative feedback
Parathyroid
cell
Parathyroid
hormone
Bone
and
kidney
Bone
resorption
Kidney
reabsorption of
calcium
Production of calcitriol
leads to intestinal
absorption of Ca2+
Plasma
[Ca2+]
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Figure 7-10
Effects of Parathyroid Hormone
 PTH release increases Ca2+ in the blood:
 Stimulates osteoclasts to digest bone matrix
 Enhances the reabsorption of Ca2+ and the secretion of
phosphate by the kidneys
 Increases absorption of Ca2+ by intestinal mucosal
 Rising Ca2+ in the blood inhibits PTH release (what type
of control is it?)
 The antagonist is the Calcitonin secreted by the thyroid
gland
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Calcitriol
 Body makes calcitriol from vitamin D
 Vitamin D can be ingested or produced in the skin
 Calcitriol causes an increase in calcium absorption in the
intestine
 Calcitriol production in the kidneys is promoted by PTH
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PTH Control of Calcium Balance
Diet
(fortified milk, fish
oil, egg yolks)
Endogenous
precursors
Sunlight
on skin
Vitamin D
Liver
25-hydroxycholecalciferol
(25(OH)D3)
Kidney
Parathyroid
hormone
Plasma
Ca2+
Calcitriol
(1,25-dihydroxycholecalciferol)
Bone,
distal nephron,
and intestine
Plasma
Ca2+
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Figure 23-20
Thyroid Gland
The thyroid gland on the anterior side of the
neck. The thyroid gland has a right lobe and
a left lobe connected by a narrow isthmus
http://webanatomy.net/histology/endocrine_histology.htm
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Calcitonin
 A peptide hormone produced by the parafollicular, or C
cells
 Lowers blood calcium levels
 Antagonist to parathyroid hormone (PTH)
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Calcitonin
 Calcitonin targets the skeleton, where it:
 Inhibits osteoclast activity (and thus bone resorption)
and release of calcium from the bone matrix
 Stimulates calcium uptake and incorporation into the
bone matrix
 Regulated by a humoral (calcium ion concentration in the
blood) negative feedback mechanism
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Hormones that are involved in water balance
 Anti diuretic hormone (ADH) – hypothalamus (stored in
the neurohypophysis)
 Aldosterone (where is it produces? What is the target
organ?)
 Atrial natriuretic peptide (ANP) - heart
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Pituitary gland (Hypophysis)
 Pituitary gland – two-lobed organ that secretes nine major
hormones
 Neurohypophysis – posterior lobe (neural tissue) and the
infundibulum
 Receives, stores, and releases hormones from the
hypothalamus
 Adenohypophysis – anterior lobe, made up of glandular
tissue
 Synthesizes and secretes a number of hormones
 Identify the 2 parts of the pituitary gland under the
microscope
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Figure 18-6a The Anatomy and Orientation of the Pituitary Gland
Third
ventricle
Median
eminence
Mamillary
body
HYPOTHALAMUS
Optic chiasm
Infundibulum
Sellar diaphragm
Anterior lobe
Pars tuberalis
Posterior
pituitary
lobe
Pars distalis
Pars intermedia
Sphenoid
(sella turcica)
Relationship of the pituitary
gland to the hypothalamus
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Pituitary-Hypothalamic Relationships: Posterior Lobe
 Is a down growth of hypothalamic neural tissue
 Has a neural connection with
(hypothalamic-hypophyseal tract)
the
hypothalamus
 Nuclei of the hypothalamus synthesize oxytocin and
antidiuretic hormone (ADH)
 These hormones are transported to the posterior pituitary
 Stores antidiuretic hormone (ADH) and oxytocin
 ADH and oxytocin are released in response to nerve
impulses
 Both use PIP-calcium second-messenger mechanism at
their targets
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HYPOTHALAMUS
1 Hormone is made and
packaged in cell body
of neuron.
2 Vesicles are transported
down the cell.
3 Vesicles containing
hormone are stored in
posterior pituitary.
POSTERIOR PITUITARY
Vein
4 Hormones are released
into blood.
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Figure 7-12, steps 1–4
Neurohypophysis hormones
Hormones that are produced in the hypothalamus and
stored in the neurohypophysis
Hormone
Target
Effect
Antidiuretic hormone
(ADH)
Kidneys
Reabsorption of water,
elevation of blood volume and pressure
(vasoconstriction)
Arginine vasopresin
(AVP)
Oxytocin (OT)
Uterus, mammary glands
(female)
Ductus deferens and prostate
gland (male)
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Labor contractions, milk ejection
Contractions of ductus deferens and
prostate gland
Antidiuretic Hormone (ADH)
 Hypothalamic osmoreceptors respond to changes in
the solute concentration of the blood
 What can cause changes in blood concentration?
 Body fluids – water
 Electrolytes – in the ECF – mainly sodium
 What is the target organ of the ADH?
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Factors Affecting ADH Release
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Figure 20-7
Water reabsorption and urine concentration
 Obligatory Water Reabsorption
 Is water movement that cannot be prevented
 Usually recovers 85% of filtrate produced
 Facultative Water Reabsorption
 Controls volume of water reabsorbed by ADH
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Aldosterone and urine concentration
 Aldosterone is a steroid secreted by the adrenal cortex
 It is secreted when blood sodium falls or if blood potassium
rises
 It is also secreted if BP drops (will be discussed later with the
urinary system)
 Aldosterone secreted – increased tubular reabsorption of
Na+ in exchange for secretion of K+ ions – water follow
 Net effect is that the body retains NaCl and water and urine
volume reduced
 The retention of salt and water help to maintain blood
pressure and volume
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Atrial natriuretic peptide (ANP) and urine volume
 Secreted from the atrial myocardium in response to high
BP
 Has 4 actions that result in the excretion of more salt and
water in the urine:
 Dilate afferent arteriole and constricts efferent – increase
GFR (more blood flow and higher GHP)
 Antagonized angiotensin-aldosterone mechanism
inhibiting both renin and aldosterone secretion
 Inhibits ADH
 Inhibits NaCl reabsorption by the collecting ducts
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by
Hormones involved in Growth and metabolism
 Growth hormone – anterior pituitary gland
 Thyroid Hormones – hypothalamus, pituitary gland and
thyroid
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The anterior lobe
 Is an out pocketing of the oral mucosa from epithelial tissue
 There is no direct neural contact with the hypothalamus
 Hormone production is regulated by the hypothalamus
 Regulatory factors from the hypothalamus arrive directly to the
adenohypophysis through the hypophyseal portal system
 Releasing hormones stimulate the synthesis and release of
hormones
 Inhibiting hormones shut off the synthesis and release of
hormones
 The hormones of the anterior pituitary (7) are called
tropic/trophic hormones because they “turn on” other glands or
organs
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Hypophyseal portal system
 Portal system - a system of blood vessels that begins and
ends in capillaries. The blood, after passing through one
capillary bed, is passing through a second capillary network.
 All blood entering the portal system will reach the target
cells before returning to the general circulation
Question – why is such a system important in the
communication between the hypothalamus and the
hypophysis?
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Pituitary-Hypothalamic Relationships: anterior Lobe
• The hypophyseal portal system,
consisting of:
• The primary capillary
plexus in the infundibulum
• The hypophyseal portal
veins
• The secondary capillary
plexus
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Tropic Hormones of the Anterior Pituitary
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The Pituitary Gland: Anterior
HYPOTHALAMIC
HORMONES
Neurons in hypothalamus
secreting trophic hormones
Dopamine*
PRFs
TRH
CRH
GHRH*
GnRH
Somatostatin
Portal system
Anterior pituitary
ANTERIOR
PITUITARY
HORMONES
Prolactin
TSH
ACTH
GH
FSH
LH
Endocrine
cells
(Gonadotropins)
ENDOCRINE TARGETS
AND THE HORMONES
THEY SECRETE
Thyroid
gland
Adrenal
cortex
Liver
Thyroid
hormones
Cortisol
IGFs
To target
tissues
Endocrine cells
of the gonads
Androgens
Estrogens,
progesterone
NONENDOCRINE
TARGETS
Breast
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Many
tissues
Germ cells
of the gonads
Figure 7-13
Normal Growth in Humans
 Growth is a continuous process that varies in rate, and
depends on four factors
1. Growth hormone and several other hormones (for
example – hormones that control calcium and glucose)
2. An adequate diet
3. Absence of chronic stress
4. Genetic potential for growth
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Growth Hormone (GH) or somatotropin
 GH is an anabolic (tissue-building) hormone
 Stimulate most body cells to increase in size and divide
by increasing protein synthesis
 Major target tissues are bone, cartilage and skeletal
muscle
 GH release is regulated factors released by the
hypothalamus:
 Growth hormone–releasing hormone (GHRH)
 Growth
hormone–inhibiting
(somatostatin
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hormone
(GHIH)
Growth Hormone Control Pathway
Circadian rhythm
Stress and cortisol
Fasting
Hypothalamus
GHRH
Anterior
pituitary
Somatostatin
GH
Liver and
other tissues
Insulin-like
growth factors
Cartilage
growth
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Blood
glucose
Bone and
tissue growth
Figure 23-13
Effects of Growth Hormone
 Growth Hormone has several distinct cellular effects
 Increases plasma glucose
 Increases bone and muscle growth
 Stimulates protein synthesis
 Stimulates liver to secrete IGFs
 IGFs stimulate cartilage growth
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Growth Hormone (GH) or somatotropin
 The stimulation of growth by GH involves 2
mechanisms:
 The primary one is indirect and more understood:
 GH influence the liver, skeletal muscle, bone, and
cartilage to release insulin-like growth factors
(IGF)/somatomedins
 The IGF binds to specific receptors on cells and
increase the uptake of amino acids and their
incorporation into new proteins
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Growth Hormone (GH) or somatotropin
 Direct effects
 In ET and CT stimulate cell division and
differentiation (the subsequent cell growth is mediated
by IGF)
 In adipose tissue GH stimulates the breakdown of
stored triglycerides by adipocytes and the release of
fatty acids to the blood. That promotes the use of fatty
acid for energy instead of the use of glucose (glucosesparing effect)
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Anterior pituitary hormones
Region
Hormone
Target
Effect
Hypothalamic
regulatory
hormone
Thyroid-stimulating
hormone (TSH/
thyrotropin)
Thyroid gland
Secretion of
thyroid
hormones (T3,
T4)
Thyrotropin-releasing
hormone (TRH)
Adrenocorticotropic
hormone (ACTH)
Adrenal cortex
(zona
fasciculate)
Secretion of
Corticotrophin-releasing
glucocorticoids
hormone (CRH)
(cortisole,
corticosterone)
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Figure 18-11b The Thyroid Follicles
Hypothalamus
releases TRH
Homeostasis
Disturbed
Decreased T3 and
T4 concentrations
in blood or low
body temperature
TRH
Anterior
lobe
Pituitary
gland
HOMEOSTASIS
Normal T3 and T4
concentrations,
normal body
temperature
Anterior
lobe
TSH
Homeostasis
Restored
Increased T3 and
T4 concentrations
in blood
Thyroid
gland
Thyroid follicles
release T3 and T4
The regulation of thyroid secretion
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Thyroid Hormone Control Pathway
Tonic release
Hypothalamus
TRH
Negative feedback
Anterior
pituitary
TSH
Thyroid
gland
T4, T3
T4
T3
KEY
Stimulus
Integrating center
Efferent pathway
Effector
Systemic response
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Systemic
metabolic
effects
Figure 23-11
Thyroid Hormone
 Thyroid hormone – major metabolic hormone
 Consists of two related iodine-containing compounds
 T4 – thyroxine; has two tyrosine molecules plus four
bound iodine atoms
 T3 – triiodothyronine; has two tyrosines with three
bound iodine atoms
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Synthesis of Thyroid Hormone
 Thyroglobulin is synthesized by the follicular cells
and released into the lumen
 Iodides (I–) are actively taken into the cell by
membrane carrier proteins
 The iodide ions diffuse to the apical surface of the
cells (these cells are facing towards…?), oxidized to
iodine (I2) by the enzyme thyroid peroxidase and
released to the colloid.
 Iodine attaches to tyrosine in the thyrogobulin,
forming T1 (monoiodotyrosine, or MIT), and T2
(diiodotyrosine, or DIT)
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Synthesis of Thyroid Hormone
 Iodinated tyrosines link together to form T3 and T4
• Coupling reaction
MIT + DIT  T3 / triiodothyronine
DIT + DIT  T4 / thyroxin (tetraiodothyronine)
 The colloid is then endocytosed and combined with a
lysosome, where T3 (10%) and T4 (90%) are cleaved
and diffuse into the bloodstream
 75% of the T4 and 70% of the T3 are transported
attached to thyroid-binding protein (TBGs) and the
rest to a special albumin
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Thyroid Hormones are Made from Iodine and
Tyrosine
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Figure 23-8
Thyroid Hormone
 Although the major thyroid hormone that is being
produced is the T4 (90%) T3 is the one responsible for the
TH effects
 Enzymes in the kidneys, liver and other tissues convert T4
to T3
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Thyroid follicle cells
Colloid
1 Thyroglobulin is synthesized and
discharged into the follicle lumen.
Tyrosines (part of thyroglobulin
molecule)
Capillary
4 Iodine is attached to tyrosine
in colloid, forming DIT and MIT.
Golgi
apparatus
Rough
ER
Iodine
3 Iodide
is oxidized
to iodine.
2 Iodide (I–) is trapped
(actively transported in).
Iodide (I–)
Lysosome
T4
T3
DIT (T2) MIT (T1)
Thyroglobulin
colloid
5 Iodinated tyrosines are
linked together to form T 3
and T4.
T4
T3
T4
T3
6 Thyroglobulin colloid is
endocytosed and combined
with a lysosome.
7 Lysosomal enzymes cleave
T4 and T3 from thyroglobulin
colloid and hormones diffuse
into bloodstream.
Colloid in
lumen of
follicle
To peripheral tissues
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Figure 16.9, step 7
Figure 18-11a The Thyroid Follicles
Follicle
cavity
Thyroglobulin
(contains T3 and T4)
FOLLICLE CAVITY
Endocytosis
Thyroglobulin
Iodide
(I+)
Other amino acids
Tyrosine
Lysosomal
digestion
T4
T3
Diffusion
TSHsensitive
ion pump
Diffusion
FOLLICLE CELL
CAPILLARY
Iodide (I–)
T4 & T3
TBG, transthryretin,
or albumin
The synthesis, storage, and secretion of thyroid hormones.
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Thyroid Hormone and target cells
 Thyroid hormones influence almost every cell of the body
 Inside the cells they bind to receptors in one of 3 locations:
 In the cytoplasm – storage of thyroid hormones to be
released if the intracellular levels decrease
 On the mitochondria surface – increase rate of ATP
production
 In the nucleus – activate genes that control the
synthesis of enzymes that involve with energy
production and utilization (for example increase of
production of sodium-potassim ATPase that uses ATP)
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Functions of Thyroid Hormones
 Elevates rates of oxygen consumption and energy consumption;
in children, may cause a rise in body temperature
 Increases heart rate and force of contraction; generally results in
a rise in blood pressure
 Increases sensitivity to sympathetic stimulation
 Stimulates red blood cell formation and thus enhances oxygen
delivery
 Stimulates activity in other endocrine tissues (E, NE for
example)
 Accelerates turnover of minerals in bone
 Activate genes that code for enzymes that are involved in
glycolysis (Glucose oxidation)
 In children, essential to normal development of Skeletal,
muscular, and nervous systems
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