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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
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Endocrine versus Nervous system
• Released in synapse
• Close to target cells
• Signal to release by action potential
• Short live effect
• Crisis management
• Released to bloodstream
• Can be distant from target cells
• Different types of signal
• Long term effect
• Ongoing processes
Neurotransmitters Hormones
• Both use chemical communication
• Both are being regulated primarily by negative feedback
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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 of calcium ions in the blood
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
Figure 16.5b
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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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Chemical structure
AA derivatives
Tyrosine:• Thyroid
hormones• Catecholamines
(Epinephrine, norepinephrine
Tryptophan:Dopamine, serotonin, melatonin
Peptides lipids
small proteins:GH,PRL
Glycoproteins:TSH, LH, FSH
short peptides:ADH, OT
Eicosanoid:prostaglandins
steroids
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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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• on the cell membranes of target cells
• In the cytoplasm or nucleus
Receptors for hormones are located:
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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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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
Proteinreceptor
G proteinactivated
Hormone
Proteinreceptor
G proteinactivated
Effects on cAMP Levels
Many G proteins, once activated, exert their effects by changing the concentrationof cyclic-AMP, which acts as the second messenger within the cell.
Increasedproduction
of cAMPadenylatecyclase
Acts assecond
messenger
kinase
Activatesenzymes
Opens ionchannels
If levels of cAMP increase,enzymes may be activatedor ion channels may beopened, accelerating themetabolic activity of the cell.
Examples:• Epinephrine and norepinephrine (β receptors)• Calcitonin• Parathyroid hormone• ADh, ACTH, FSH, LH, TSH• Glucagon
Examples:• Epinephrine and norepineph- rine (α2 receptors)
In some instances, G proteinactivation results in decreasedlevels of cAMP in thecytoplasm. This decrease hasan inhibitory effect on the cell.
Enhancedbreakdown
of cAMPPDE
Reducedenzymeactivity
Hormone
Proteinreceptor
G protein(inactive)
G proteinactivated
Copyright © 2010 Pearson Education, Inc. Figure 16.2, step 5
Hormone (1st messenger)binds receptor.
Receptoractivates Gprotein (GS).
G proteinactivatesadenylatecyclase.
cAMP acti-vates proteinkinases.
Adenylatecyclaseconverts ATPto cAMP (2ndmessenger).
Receptor
G protein (GS)
Adenylate cyclase
Triggers responses oftarget cell (activatesenzymes, stimulatescellular secretion,opens ion channel,etc.)
Hormones thatact via cAMPmechanisms:
EpinephrineACTHFSHLH
Inactiveprotein kinase
Extracellular fluid
Cytoplasm
Activeproteinkinase
GDP
GlucagonPTHTSHCalcitonin
1
2 3 4
5
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• Hormone binds to the receptor and activates G protein
• 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
Amino Acid-Based Hormone Action: PIP-Calcium
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GTP PIP2
IP3
ReceptorGTP
GTP
CatecholaminesTRHADHGnRHOxytocin
Triggers responses of target cell
GDP
Extracellular fluid
Cytoplasm
Inactiveprotein kinase C
Activeprotein kinase C
Phospholipase C
Gq
Ca2+ Ca2+- calmodulin
Hormone
Endoplasmicreticulum
DAG1
2 34 5
5
6
Figure 16.3
Amino Acid-Based Hormone Action: PIP Mechanism
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Hormone
Proteinreceptor
G protein(inactive)
G proteinactivated
Hormone
Proteinreceptor
G proteinactivated
Effects on Ca2+ Levels
Some G proteins use Ca2+ as asecond messenger.
Examples:
• Epinephrine and norepinephrine (α1 receptors)
• Oxytocin• Regulatory hormones of hypothalamus• Several eicosanoids
Activatesenzymes
Calmodulin
PLC,DAG,and IP3
Opening of Ca2+ channels
Release ofstored Ca2+
from ER or SER
Ca2+ acts assecond messenger
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Steroid Hormones: Action
Figure 7-7, steps 1–5
1
Cellmembrane
Interstitialfluid
Cytoplasmicreceptor
Endoplasmicreticulum
Nucleus
Nuclear receptor
DNA
Translation
Cell surface receptor
Rapid responses
Transcriptionproduces mRNA
Steroid hormone
Bloodvessel
Proteincarrier
Newproteins
Steroid hormone receptors are in thecytoplasm or nucleus.
Most hydrophobic steroids are bound toplasma protein carriers. Only unboundhormones can diffuse into the target cell.
Translation produces new proteinsfor cell processes.
Some steroid hormones also bind to membrane receptors that use secondmessenger systems to create rapidcellular responses.
The receptor-hormone complex binds toDNA and activates or represses one ormore genes.
Activated genes create new mRNA thatmoves back to the cytoplasm.
2a
2
54
3
1
2a
2
3
4
5
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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)
Steroids and thyroid hormones
Alter transcriptional activity of responsive genes
http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/moaction/change.html
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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
HOMEOSTASISDISTURBED
Rising bloodglucose levels
Beta cellssecreteinsulin.
Ris
ing
blo
od
glu
cose
lev
els
Fal
lin
g b
loo
d g
luco
se l
evel
s
Falling bloodglucose level
HOMEOSTASISDISTURBED
Alpha cellssecrete
glucagon
HOMEOSTASISRESTORED
HOMEOSTASISRESTORED
Blood glucoselevels decrease
Blood glucose levels increase
Increased breakdown ofglycogen to glucose (inliver, skeletal muscle)
Increased breakdown of fat to fatty acids (inadipose tissue)
Increased synthesisand release of glucose(in liver)
HOMEOSTASIS
Normal bloodglucose levels(70-110 mg/dL)
Increased amino acidabsorption and proteinsynthesis
Increased triglyceridesynthesis in adiposetissue
Increased conversionof glucose to glycogen
Increased rate ofglucose utilization andATP generation
Increased rate ofglucose transport intotarget cell
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Endocrine Reflex Pathways: Insulin release
Figure 7-9
Receptor
Efferent path
Effector
Tissue response
Stimulus
Efferent neuron
Sensory neuron
Integrating center
Systemic response
KEY
Eat a meal
Pancreas
Insulin
Stretch receptorin digestive tract
Glucose uptakeand utilization
CNS
Targettissues
Bloodglucose
Afferent neuron
Efferent neuron
Blood glucose
Neg
ativ
e fe
edba
ck
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• 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 (insulin-dependant 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.
Effects of Insulin Binding to its receptors
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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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• 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
Glucagon
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• 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
Adrenal (Suprarenal) Glands
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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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Immunesystem Liver
Functionsuppressed
Gluco-neogenesis
Proteincatabolism
MuscleAdipose
tissue
Lipolysis
CRH
ACTH
Cortisol
Hypothalamus
Anteriorpituitary
Adrenalcortex
Circadianrhythm
Stress
lon
g-lo
op n
egat
ive
feed
bac
k
Pathway For the Control of Cortisol Secretion
Figure 23-3
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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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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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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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• 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+
Zona glomerulosa - Mineralocorticoids
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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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[free Ca2+]0.001 mM
Kidney
Ca2+
in urine
Ca2+
PassivefiltrationCalcitonin
Small intestine
Dietarycalcium
Ca2+Ca2+ inkidneytubules
PTH
Calcitonin
Calcitriol(PTH, prolactin)
PTH
CalcitriolCortisol
Electrochemicalgradient
Activetransport
Bone
* Some calcium is secretedinto the small intestine.
Cells
ECF
PTH = parathyroid hormoneKEY
Calciumin feces
[Ca2+]2.5 mM
Figure 23-17
Body Calcium is Carefully Regulated
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Simple Endocrine Reflex: Parathyroid Hormone
Figure 7-10
Bone and
kidney
Low plasma
[Ca2+]
Plasma
[Ca2+]
Bone resorption
Kidneyreabsorption of
calcium
Parathyroid cell
Parathyroid hormone
Production of calcitriolleads to intestinalabsorption of Ca2+
Negative feedback
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• 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
Effects of Parathyroid Hormone
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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
Figure 23-20
PlasmaCa2+
Vitamin D
Endogenousprecursors
Diet(fortified milk, fish
oil, egg yolks)
Liver
25-hydroxycholecalciferol(25(OH)D3)
Calcitriol(1,25-dihydroxycholecalciferol)
Bone,distal nephron, and intestine
Kidney
PlasmaCa2+
Parathyroidhormone
Sunlighton skin
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• A peptide hormone produced by the parafollicular, or C cells
• Lowers blood calcium levels
• Antagonist to parathyroid hormone (PTH)
Calcitonin
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• 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
Calcitonin
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Hormones that are involved in water balance
Anti diuretic hormone (ADH) – hypothalamus (stored in the neurohypophysis)
Aldosterone
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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Pituitary-Hypothalamic Relationships: Posterior Lobe
• Is a down growth of hypothalamic neural tissue
• Has a neural connection with the hypothalamus (hypothalamic-hypophyseal tract)
• 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
Copyright © 2010 Pearson Education, Inc. Figure 7-12, steps 1–4
HYPOTHALAMUS
Vein
POSTERIOR PITUITARY
Vesicles are transported down the cell.
Vesicles containing hormone are stored in posterior pituitary.
Hormones are releasedinto blood.
Hormone is made and packaged in cell body of neuron.
1
2
3
4
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Neurohypophysis hormones
Hormone Target Effect
Antidiuretic hormone (ADH)
Arginine vasopresin (AVP)
Kidneys Reabsorption of water,
elevation of blood volume and pressure (vasoconstriction)
Oxytocin (OT) Uterus, mammary glands (female)
Ductus deferens and prostate gland (male)
Labor contractions, milk ejection
Contractions of ductus deferens and prostate gland
Hormones that are produced in the hypothalamus and stored in the neurohypophysis
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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
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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 by inhibiting both renin and aldosterone secretion
• Inhibits ADH
• Inhibits NaCl reabsorption by the collecting ducts
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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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• 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?
Hypophyseal portal system
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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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The Pituitary Gland: Anterior
Figure 7-13
HYPOTHALAMIC HORMONES
ANTERIOR PITUITARYHORMONES
NONENDOCRINETARGETS
ENDOCRINE TARGETSAND THE HORMONESTHEY SECRETE
Somatostatin
GHRH* GnRH
Portal system
Anterior pituitary
FSH LH
Neurons in hypothalamussecreting trophic hormones
To target tissues
GH
Endocrine cellsof the gonads
Endocrinecells
Many tissues
Germ cellsof the gonads
Thyroid gland
Thyroid hormones
Adrenalcortex
Cortisol
Liver
IGFs AndrogensEstrogens,
progesterone
PRFs TRH CRH
TSH ACTHProlactin
Breast
Dopamine*
(Gonadotropins)
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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 hormone (GHIH) (somatostatin
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SomatostatinGHRH
GH
Hypothalamus
Liver andother tissues
Insulin-likegrowth factors
Anteriorpituitary
Circadian rhythmStress and cortisol
Fasting
Bone andtissue growth
Cartilagegrowth
Bloodglucose
Growth Hormone Control Pathway
Figure 23-13
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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 (glucose-sparing 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 glucocorticoids (cortisole, corticosterone)
Corticotrophin-releasing hormone (CRH)
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Figure 18-11b The Thyroid Follicles
The regulation of thyroid secretion
HomeostasisDisturbed
HOMEOSTASIS
HomeostasisRestored
Thyroid folliclesrelease T3 and T4
Thyroidgland
TSH
Anteriorlobe
Pituitarygland
Hypothalamusreleases TRH
TRH
Anteriorlobe
Decreased T3 and T4 concentrationsin blood or lowbody temperature
Normal T3 and T4 concentrations,
normal bodytemperature
Increased T3 and T4 concentrationsin blood
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TSH
T4, T3
T4 T3
Hypothalamus
Anteriorpituitary
Thyroidgland
Systemicmetabolic
effects
Stimulus
Integrating center
Efferent pathway
Effector
Systemic response
TRH
Tonic release
KEY
Negative feed
back
Thyroid Hormone Control Pathway
Figure 23-11
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• 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
Thyroid Hormone
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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
Figure 23-8
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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
Copyright © 2010 Pearson Education, Inc. Figure 16.9, step 7
To peripheral tissues
T3
T3
T3
T4
T4
Lysosome
Tyrosines (part of thyroglobulinmolecule)
T4
DIT (T2)Iodine
MIT (T1)
Thyro-globulincolloid
Iodide (I–)
RoughER
Capillary
Colloid
Colloid inlumen offollicle
Thyroid follicle cells
Iodinated tyrosines arelinked together to form T3
and T4.
Iodideis oxidizedto iodine.
Thyroglobulin colloid isendocytosed and combinedwith a lysosome.
Lysosomal enzymes cleaveT4 and T3 from thyroglobulincolloid and hormones diffuseinto bloodstream.
Iodide (I–) is trapped(actively transported in).
Thyroglobulin is synthesized anddischarged into the follicle lumen.
Iodine is attached to tyrosinein colloid, forming DIT and MIT.
Golgiapparatus
1
2
3
4
5
6
7
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Figure 18-11a The Thyroid Follicles
Folliclecavity
Thyroglobulin(contains T3 and T4)
FOLLICLE CAVITY
Endocytosis
Lysosomaldigestion
Thyroglobulin
Other amino acids
Tyrosine
Diffusion
DiffusionTSH-sensitiveion pump FOLLICLE CELL
CAPILLARY
Iodide (I–)
T4 & T3
TBG, transthryretin,or albumin
The synthesis, storage, and secretion of thyroid hormones.
Iodide(I+)
T4T3
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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)