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The Endocrine System
Chapter 46
2
Types of Chemical Messengers
A hormone is a chemical that is secreted into extracellular fluid and carried by the blood
-Can therefore act at a distance from source
-Only targets with receptor can respond
Paracrine regulators do not travel in blood
-Allow cells of organ to regulate each other
Pheromones are chemicals released into the environment to communicate among individuals of a single species
3
Types of Chemical Messengers
Some neurotransmitters are distributed by the blood and act as neurohormones
-Norepinephrine coordinates the activity of heart, liver and blood vessels during stress
Hormone production and release is often regulated directly or indirectly by the nervous system
4
Axon
Neurotransmitters
Glands
Paracrine secretion
Hormonescarried by blood
Target cell
Extracellularspace
Receptorproteins
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5
Endocrine System
The endocrine system includes all the organs and tissues that produce hormones
-Includes endocrine glands, which are specialized to secrete hormones
-Also organs, like the liver, that secrete hormones in addition to other functions
Exocrine glands secrete their products, such as saliva or milk, into a duct for transport to the outside
6
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Ovaries (in females)
Parathyroid glands(behind thyroid)
Hypothalamus Pineal gland
NeurohypophysisPituitarygland
Thyroid gland
Thymus
Adrenalglands
Pancreas
Testes(in males)
Adenohypophysis
7
Classes of Hormones
Molecules that function as hormones must exhibit two basic characteristics
1. Must be sufficiently complex to convey regulatory information to their target cells
2. Must be adequately stable to resist destruction before reaching their target cells
Three chemical classes meet these requirements
8
Classes of Hormones
1. Peptides and proteins-Glycoproteins
2. Amino acid derivatives-Catecholamines-Thyroid hormones-Melatonin
3. Steroids-Sex steroids-Corticosteroids
9
Classes of Hormones
Hormones may be categorized as:
-Lipophilic (nonpolar) = fat-soluble
-Steroid hormones and thyroid hormones
-Bind to intracellular receptors
-Hydrophilic (polar) = water-soluble
-All other hormones
-Bind to extracellular receptors
105
33
44
1 1
2
LipophilicHydrophilic
Endocrine gland A Endocrine gland B
1. Hormones secreted into extracellular fluid and diffuse into
2. Hormones distributed by blood to all cells. Diffuse from blood to extracellular fluid.
3. Nontarget cells lack receptors, and cell stimulation does not occur.
4. Target cells possess receptors, and are activated by hormones.
5. Unused, deactivated hormones are removed by the liver and kidney.
Secretoryvesicles Hormones
Hormones
Transport proteins
Membranereceptors
Target cell Target cell
ActivatedActivated
Nuclearreceptor
Nontargetcells
Nontargetcells
Extracellularfluid
Extracellularfluid
Bloodvessels
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11
Paracrine Regulators
Paracrine regulation occurs in most organs
-Growth factors are proteins that promote growth and cell division in specific organs
-Epidermal growth factor = Skin
-Nerve growth factor = Neurons
-Insulin-like growth factor = Bone
-Cytokines = Immune system
12
Paracrine Regulators
The endothelium of blood vessels is a rich source of paracrine regulators
-Nitric oxide (NO) which promotes vasodilation
-Endothelin which stimulates vasoconstriction
-Bradykinin which promotes vasodilation
13
Paracrine Regulators
Prostaglandins
-A diverse group of fatty acids that are produced in almost every organ
-Regulate a variety of functions including:
-Smooth muscle contraction, lung function, labor, and inflammation
-Synthesis is inhibited by nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen
14
Lipophilic Hormones
Lipophilic hormones include the steroid hormones (derived from cholesterol) and the thyroid hormones (tyrosine + iodine)
-As well as the retinoids, or vitamin AThyroxineCortisol (Hydrocortisone)
O
HO OHH3C
CH2OH
C O
HO O
I I
I I NH2
CH2
COOH
H3C
Testosterone
O
OH
H3C
H3C
CH
15
Lipophilic Hormones
These hormones circulate in the blood bound to transport proteins
-Dissociate from carrier at target cells
-Pass through the cell membrane and bind to an intracellular receptor, either in the cytoplasm or the nucleus
-Hormone-receptor complex binds to hormone response elements in
DNA
-Regulate gene expression
16
Receptor
Bloodplasma
Protein
Lipophilic hormones
mRNA
DNA
Hormone response element
1. Hormone passes through plasma membrane
2. Inside target cell the hormone binds to a receptor protein in the cytoplasm or nucleus
3. Hormone-receptor complex binds to hormone response element on DNA, regulating gene transcription
4. Protein synthesis
5. Change in protein synthesis is cellular response
Cytoplasm
Plasma membrane
Nucleus
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17
Hydrophilic Hormones
Hydrophilic hormones include the peptide, protein and catecholamine hormones
-Too large or polar to cross cell membrane
Hormones bind to extracellular receptors
-Initiate signal transduction pathways
1. Activation of protein kinases
2. Production of second messengers
18
Hormone
InactiveActive kinasedomain
Receptor
Targetprotein
P
P P P
Phosphorylatedprotein
GPCR
Inactive Gprotein
Active Gprotein
Second messenger-generating enzyme
Hormones
GTPGTPGDP
GPCR
Inactiveprotein kinase
Targetproteins
ActiveProteinkinase
Secondmessenger
1. Receptors Function as Kinase Enzymes 2. Receptors Activate G Proteins
Cellularresponse
ADP
Cellularresponse
ATP
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19
Hydrophilic Hormones
Receptor kinases
-For some peptide hormones (like insulin) the receptor itself is a kinase
-Can directly phosphorylate intracellular proteins that alter cellular activity
-For other peptide hormones (like growth hormone) the receptor itself is not a kinase
-Rather, it activates intracellular kinases
20
Hydrophilic Hormones
Second-messenger systems
-Many hydrophilic hormones work through second messenger systems
-Two have been described:
-One involving cyclic adenosine monophosphate (cAMP)
-One that generates 2 lipid messengers: inositol triphosphate (IP3) and diacyl glycerol (DAG)
21
Hydrophilic Hormones
Second-messenger systems
-Receptors are linked to a second-messenger-generating enzyme via membrane proteins called G proteins
-Are thus called G-protein-coupled receptors (GPCP)
-When the G protein activates the enzyme, the second-messenger molecules increase
22
The Pituitary Gland
The pituitary gland is also known as the hypophysis
-It hangs by a stalk from the hypothalamus
The pituitary gland consists of two parts:
-Anterior pituitary (adenohypophysis)
-Appears glandular
-Posterior pituitary (neurohypophysis)
-Appears fibrous
23
The Posterior Pituitary
The posterior pituitary develops from growth of the brain
-It remains directly connected to the hypothalamus by a tract of axons
It stores and releases two hormones, that are actually produced by neuron cell bodies in the hypothalamus
-Neuroendocrine reflex
24
The Posterior Pituitary
Antidiuretic hormone (ADH)
-A peptide hormone that stimulates water reabsorption by the kidney, and thus inhibits diuresis (urine production)
Oxytocin
-Like ADH, it is composed of 9 amino acids
-In mammals, it stimulates the milk ejection reflex and uterine contractions during labor, and it regulates reproductive behavior
25• ADH increases vasoconstriction
• ADH reduces urine volume
Effector
ADH synthesizedby neurosecretory
cells in thehypothalamus
is releasedfrom neuro-
hypophysis intoblood
Integrating Center
Water returned toblood
Response
Increasesblood pressure
Response
Osmoticconcentration ofblood increases
Stimulus
Dehydration
Stimulus
Lowers bloodvolume and
pressure
Stimulus
Osmoreceptorsin CNS monitorconcentration
Sensor
Baroreceptorsin aorta
monitor pressure
Sensor
( – )
Negativefeedback
( – )
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Effector
Negativefeedback
26
The Anterior Pituitary
The anterior pituitary develops from a pouch of epithelial tissue of the embryo’s mouth
It produces at least seven essential hormones
-Collectively called tropic hormones or tropins
-Can be categorized into three families
-Peptide hormones, protein hormones and glycoprotein hormones
27
The Anterior Pituitary
Peptide hormones
-Fewer than 40 amino acids in size
-Adrenocorticotropic hormone (ACTH)
-Melanocyte-stimulating hormone (MSH)
Protein hormones
-A single chain of about 200 amino acid
-Growth hormone (GH)
-Prolactin (PRL)
28
The Anterior Pituitary
Glycoprotein hormones
-Dimers, containing alpha () and beta () subunits, each around 100 amino acids
-Thyroid-stimulating hormone (TSH)
-Luteinizing hormone (LH)
-Follicle-stimulating hormone (FSH)
29
The Anterior Pituitary
The activity of the anterior pituitary is controlled by hormones of the hypothalamus
-Neurons secrete releasing hormones and inhibiting hormones, which diffuse into blood capillaries at the hypothalamus’ base
-Each hormone delivered by the hypothalamohypophysial portal system regulates a specific anterior pituitary hormone
30
Portal veins
Hypothalamus
AdenohypophysisSecondary capillaries
Neurohypophysis
Primary capillaries
Primarycapillaries
Axons to primarycapillaries
Neuron cellbodies
Axons to primarycapillaries
Hormones
Portal veins
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31
The Anterior Pituitary
The hypothalamus and the anterior pituitary are partially controlled by the very hormones whose secretion they stimulate
-This is termed negative feedback or feedback inhibition
Positive feedback is uncommon because it causes deviations from homeostasis
-One example is the control of ovulation
32
Tropic hormones(TSH, ACTH, FSH, LH)
Adenohypophysis
Thyroid, adrenalcortex, gonads
Target Glands
Hormones
Releasing hormones(TRH, CRH, GnRH)
Hypothalamus
( + )
( + )
( + )
Targetcells
( – )
( – )
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Negativefeedback
33
The Anterior Pituitary
The anterior pituitary is sometimes referred to as the “master gland”
-Its effects may be direct or indirect
-Direct: activation of nonendocrine targets
-Indirect: activation of other endocrine glands
Hypophysectomy is the surgical removal of the pituitary
34
Anterior Pituitary Disorders
Growth hormone stimulates growth of muscles and connective tissue
-It also promotes the production of insulin-like growth factors
-Stimulate cell division in the epiphyseal growth plates, and thus bone elongation
Gigantism is caused by an excessive secretion of growth hormone in a child
35
Anterior Pituitary Disorders
36
Anterior Pituitary Disorders
In contrast, pituitary dwarfism is caused by a deficiency in GH secretion during childhood
GH can no longer cause an increase in height in adults because human skeletal plates transform from cartilage into bone at puberty
-Excessive GH secretion in an adult results in acromegaly
37
The Thyroid Gland
In humans, the thyroid gland is shaped like a bow tie, and lies just below the Adam’s apple in the front of the neck
-It secretes:
-Thyroid hormones
-Thyroxine
-Triiodothyronine
-Calcitonin
38
The Thyroid Gland
Thyroid hormones bind to nuclear receptors
-Regulate carbohydrate & lipid metabolism
-Adults with hypothyroidism have low production of thyroxine
-Reduced metabolism and overweight
-Adults with hyperthyroidism have high production of thyroxine
-High metabolism and weight loss
-Trigger metamorphosis in amphibians
39
Th
yro
xin
e p
rod
uc
tio
n
–35 –30 –25 –20 –15
Days from emergence of forelimb
–10 –5 0 +5 +10 +20
TSH stimulates thyroid to producethyroxine.
Forelimbs emerge.
Tail is reabsorbed.
Hypothalamusstimulatesadenohypophysis tosecrete TSH.
Rapid growth Reduced growth,rapid differentiation
Rapid differentiation
Premetamorphosis Prometamorphosis Climax
Receptor stimulation
Hypothalamus stimulation
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40
The Thyroid Gland
Calcitonin
-A peptide hormone
-Stimulates the uptake of calcium (Ca2+) into bones
-Thus, lowering its levels in the blood
41
The Parathyroid Glands
The parathyroid glands are four small glands attached to the thyroid
-Produce parathyroid hormone (PTH) in response to falling levels of Ca2+ in blood
-Stimulates osteoclasts to dissolve calcium phosphate crystals in the bone matrix and release Ca2+ into blood
-Stimulates the kidneys to reabsorb Ca2+ from the urine
42
The Parathyroid Glands
PTH also indirectly leads to the absorption of Ca2+ from food in the intestines by its activation of vitamin D
-Vitamin D is produced in the skin from a cholesterol derivative in response to UV light
-It diffuses into blood in an inactive form
-Activated by an enzyme that is stimulated by PTH
43Increasedblood Ca2+
Response
Low blood Ca2+
Stimulus
Parathyroid glands
Parathyroid
SecretesPTH
( + )( + ) ( + )
( – )
Osteoclastsdissolve Ca(PO4)2
crystals in bone,releasing Ca2+
Effector
Reabsorption ofCa2+, excretion
of PO43–
Increasedabsorption of Ca2+
from intestine (dueto PTH activation
of vitamin D)
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EffectorEffector
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44
The Adrenal Glands
The adrenal glands are located just above each kidney
-Medulla = Inner portion
-Stimulated by the sympathetic division of the autonomous nervous system
-Cortex = Outer portion
-Stimulated by the anterior pituitary, through the hormone ACTH
45
The Adrenal Glands
The medulla secretes the catecholamines epinephrine and norepinephrine
-These trigger “alarm” responses helping the body prepare for extreme efforts
-Lead to an increase in: heart rate, blood pressure, blood glucose level, and
blood flow to heart and muscle
46
The Adrenal Glands
The cortex secretes steroid hormones called corticosteroids
-Glucocorticoids (such as cortisol) maintain glucose homeostasis and modulate some aspects of the immune response
-Mineralocorticoids (such as aldosterone) regulate mineral balance by stimulating the kidneys to reabsorb Na+ and excrete K+
47
Sympathetic nervoussystem
Sympatheticaxons
Adrenal medullaAdrenal cortex
Adenohypophysis
EffectorCatecholamine HormonesGlucocorticoids
ACTH secreted fromthe adenohypophysis
• Longer term stress response.
( + )
StressStimulus
( – )
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Effector
• Effects on lipid and carbohydrate metabol- ism, immune system, and damage repair.
• Short term stress response.• Effects on cardiovascular system, carbohydrate and lipid metabolism, central nervous system.
Negativefeedback
48
The Pancreas
The pancreas is located adjacent to stomach
-Connected to the duodenum of the small intestine by the pancreatic duct
The islets of Langerhans are scattered clusters of cells throughout the pancreas
-These govern blood glucose levels through two hormones with antagonistic functions
49
The Pancreas
Insulin
-Secreted by beta () cells of the islets
-Stimulates cellular uptake of blood glucose and its storage as glycogen in the liver and muscle cells or as fat in fat cells
Glucagon
-Secreted by alpha () cells of the islets
-Promotes the hydrolysis of glycogen in the liver and fat in adipose tissue
50
( + )
( – )( – )
( + )
Blood glucose increased
Stimulus
Blood glucose decreased
StimulusAfter a Meal Between Meals
Effector
Increased glucagonproductionby cells
Effector
Increased insulinproductionby cells
Response
Glycogen hydrolyzed toglucose, then secreted into
blood, increasing blood glucose
Response
Glucose moves fromblood into cells,
reducing blood glucose
Sensor
PancreaticIslets
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Diabetes Mellitus
Diabetics cannot take up glucose from blood
-Type I (insulin-dependent diabetes)
-Individuals lack insulin-secreting cells
-Treated by daily injections of insulin
-Type II (noninsulin-dependent diabetes)
-Most patients have this form
-Very low number of insulin receptors
-Treated by diet and exercise
52
The Gonads
The ovaries and testes in vertebrates
-Produce sex steroids that regulate reproductive development
-Estrogen and progesterone
-“Female” hormones
-Androgens
-“Male” hormones
-Testosterone and its derivatives
53
The Pineal Gland
The pineal gland is located in the roof of the third ventricle of the brain
-Functions as an endocrine gland by secreting the hormone melatonin
-Reduces dispersal of melanin granules
-Regulates biological clocks
-Synchronizes various body processes to a circadian rhythm
54
Other Hormones
Some hormones are secreted by organs that are not exclusively endocrine glands
-Atrial natriuretic hormone is secreted by the right atrium of the heart
-Promotes salt and water excretion
-Erythropoietin is secreted by the kidney
-Stimulates the bone marrow to produce red blood cells
55
Insect Hormones
Insects undergo two types of transformations during post-embryonic development
-Molting = Shedding of old exoskeleton and secretion of a new larger one
-Metamorphosis = Radical transformation from the larval to the adult form
56
Insect Hormones
Hormonal secretions influence both molting and metamorphosis
-Brain hormone stimulates prothoracic gland to produce ecdysone, or molting hormone
-High levels cause molting
-The corpora allata produce a hormone called the juvenile hormone
-Low levels result in metamorphosis
57
Neurosecretory cells
Larval molt Pupal molt Adult molt
Corpora allata
Prothoracicgland
Brain hormone
Juvenile hormone
Ecdysone
Lowamounts
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