Introduction to the Endocrine System - Professor Welday's...

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Introduction to the Endocrine System

Chapter 7a

1

About This Chapter

• Hormones

• The classification of hormones

• Control of hormone release

• Hormone interactions

• Endocrine pathologies

• Hormone evolution


2

Hormones: Function

• Control – Rates of enzymatic reactions

– Transport of ions or molecules across cell membranes

– Gene expression and protein synthesis


3 Figure 7.1 An endocrine disorder in ancient art 4

Figure 7.2-2 ANATOMY SUMMARY – Hormones

KEYG ==== glandC ==== endocrine cellsN ==== neurons

P ==== peptideS ==== steroidA ==== amino acid–derived

Pineal gland

Hypothalamus (N)

Posteriorpituitary (N)

Anterior pituitary (G)

Melatonin [A]

Trophic hormones [P] (see Fig. 7.8)

Oxytocin [P]

Vasopressin (ADH) [P]

Prolactin [P]

Luteinizing hormone [P]

Growth hormone (somatotropin) [P]

Follicle-stimulating hormone [P]

Corticotropin (ACTH) [P]

Thyrotropin (TSH) [P]

Brain, other tissues

Anterior pituitary

Breast and uterus

Kidney

Breast

LiverMany tissues

Adrenal cortex

Thyroid gland

Gonads

Gonads Sex hormone production; egg or sperm production

Egg or sperm production; sex hormone production

Thyroid hormone synthesis

Cortisol release

Growth and metabolismGrowth factor secretion

Milk production

Water reabsorption

Milk ejection; labor and delivery; behavior

Release or inhibit pituitary hormones

Circadian rhythms; immune function; antioxidant

Main Effect(s)Primary Target(s)HormoneLocation

5 Figure 7.2-3 ANATOMY SUMMARY – Hormones




Thyroid gland

Parathyroid gland

Thymus gland

Heart (C)

Liver (C)

Stomach andsmall intestine (C)

Pancreas (G)

Triiodothyronine and thyroxine [A]

Calcitonin [P]

Parathyroid hormone [P]

Thymosin, thymopoietin [P]

Atrial natriuretic peptide [P]

Angiotensinogen [P]

Insulin-like growth factors [P]

Gastrin, cholecystokinin,secretin, and others [P]

Insulin, glucagon, somatostatin,pancreatic polypeptide [P]

Many tissues

Many tissues

Many tissues

Bone

Bone, kidney

Lymphocytes

Kidneys

Adrenal cortex, blood vessels

GI tract and pancreas

Metabolism, growth, and development

Plasma calcium levels (minimal effect in humans)

Regulates plasma Ca 2+ and phosphate levels

Lymphocyte development

Increases Na + excretion

Aldosterone secretion; increases blood pressure

Growth

Assist digestion and absorption of nutrients

Metabolism of glucose and other nutrients

6

Figure 7.2-4 ANATOMY SUMMARY – Hormones




Adrenal cortex (G)

Adrenal medulla (N)

Kidney (C)

Skin (C)

Aldosterone [S]Cortisol [S]Androgens [S]

Epinephrine, norepinephrine [A]

Erythropoietin [P]

1,25 Dihydroxy-vitamin D 3(calciferol) [S]

Vitamin D 3 [S]

KidneyMany tissues

Many tissues

Many tissues

Bone marrow

Intestine

Intermediate form of hormone

Na+ and K + homeostasisStress response

Sex drive in females

Fight-or-flight response

Red blood cell production

Increases calcium absorption

Precursor of 1,25 dihydroxy-vitamin D 3

7 Figure 7.2-5 ANATOMY SUMMARY – Hormones




Testes (male) (G)

Ovaries (female) (G)

Adipose tissue (C)

Placenta (pregnantfemales only) (C)

Androgens [S]

Inhibin [P]

Estrogen, progesterone [S]

Inhibin [P]

Relaxin (pregnancy) [P]

Leptin, adiponectin, resistin

Estrogen, progesterone [S]

Chorionic somatomammotropin [P]

Chorionic gonadotropin [P]

Many tissues

Many tissues

Many tissues

Many tissues

Anterior pituitary

Anterior pituitary

Uterine muscle

Hypothalamus, other tissues

Corpus luteum

Sperm production, secondary sex characteristics

Inhibits FSH secretion

Egg production, secondary sex characteristics

Inhibits FSH secretion

Relaxes muscle

Food intake, metabolism, reproduction

Fetal, maternal development

Metabolism

Hormone secretion

8

Figure 7.2-1 ANATOMY SUMMARY – Hormones 9

Hormones

• Cell-to-cell communication molecules– Chemical signals

– Secreted by a cell or group of cells

– Transported by blood

– Distant target tissue receptors

– Activates physiological response at low concentrations

• Pheromones: elicit physiological or behavioral response on other organisms of the same species


10

Hormones

• Cellular mechanism of action– Depends on binding to target cell receptors

– Initiates biochemical responses

• Half-life indicates length of activity


11

Hormones: Classification by Chemical Class

• Peptide or protein hormones

• Steroid hormones

• Amino acid–derived or amine hormones


12

Table 7.1 Comparison of Peptide, Steroid, and Amino Acid-Derived Hormones 13

Hormones: Peptides or Proteins

• Preprohormone– Large, inactive precursor

• Prohormone– Smaller, inactive

– Proteolytic, post-translational modification

• Peptide/protein hormones– Bind surface membrane receptors

– Cellular response through signal transduction system


14

Figure 7.3 ESSENTIALS – Peptide Hormone Synthesis an d Processing 15 Figure 7.3 ESSENTIALS – Peptide Hormone Synthesis an d Processing

mRNA

Preprohormone Ribosome

Endoplasmicreticulum (ER)

Cytoplasm

ECF

Plasma Capillaryendothelium

Messenger RNA onthe ribosomes bindsamino acids into apeptide chain called apreprohormone. Thechain is directed intothe ER lumen by asignal sequence ofamino acids.

Slide 1


16

Figure 7.3 ESSENTIALS – Peptide Hormone Synthesis an d Processing

mRNA

Preprohormone

Signalsequence

Prohormone

Ribosome


Cytoplasm

ECF


Enzymes in the ERchop off the signalsequence, creating aninactive prohormone.


Slide 2


17 Figure 7.3 ESSENTIALS – Peptide Hormone Synthesis an d Processing

mRNA

Preprohormone

Signalsequence

Prohormone

Ribosome


Transportvesicle

Golgicomplex

Cytoplasm

ECF




The prohormonepasses from the ERthrough the Golgicomplex.

Slide 3


18


mRNA

Preprohormone

Signalsequence

Prohormone

Ribosome


Transportvesicle

Golgicomplex

Cytoplasm

ECF

Plasma

Secretoryvesicle

Capillaryendothelium

Peptide fragment

Active hormone




Secretory vesiclescontaining enzymesand prohormone budoff the Golgi. Theenzymes chop theprohormone into oneor more activepeptides plusadditional peptidefragments.

Slide 4


19 Figure 7.3 ESSENTIALS – Peptide Hormone Synthesis an d Processing

mRNA

Preprohormone

Signalsequence

Prohormone

Ribosome


Transportvesicle

Golgicomplex

Cytoplasm

ECF

Plasma

Secretoryvesicle

Releasesignal

Capillaryendothelium

Peptide fragment

Active hormone





The secretory vesiclereleases its contentsby exocytosis into theextracellular space.

Slide 5


20


mRNA

Preprohormone

Signalsequence

Prohormone

Ribosome


Transportvesicle

Golgicomplex

Cytoplasm

ECF

Plasma

Secretoryvesicle

Releasesignal

Capillaryendothelium To target

Peptide fragment

Active hormone





The secretory vesiclereleases its contentsby exocytosis into theextracellular space.

The hormone movesinto the circulation fortransport to its target.

Slide 6


21 Figure 7.3a ESSENTIALS – Peptide Hormone Synthesis a nd Processing

Preprohormones

Preprohormone

PreproTRH (242 amino acids)

6 TRH(3 amino acids each)

Other peptide fragments

Signal sequence

processes to

PreproTRH (thyrotropin-releasinghormone) has six copies of the3-amino acid hormone TRH.

22

Figure 7.3b ESSENTIALS – Peptide Hormone Synthesis a nd Processing

Prohormones

Pro-opiomelanocortin

Prohormones, such as pro-opiomelanocortin, the prohormone forACTH, may contain several peptidesequences with biological activity.

ACTH

Peptide fragment

γγγγ lipotropin ββββ endorphin

processes to

23 Figure 7.3c ESSENTIALS – Peptide Hormone Synthesis a nd Processing

Prohormones Process to Active Hormone Plus Peptide Fragments

Proinsulin

Insulin C-peptideprocesses to

The peptide chain ofinsulin’s prohormonefolds back on itself withthe help of disulfide(S—S) bonds. Theprohormone cleaves toinsulin and C-peptide.

24

Endocrine System Review


Interactive Physiology® Animation: Endocrine System: Endocrine System Review

25 Figure 7.4 Membrane receptors and signal transducti on for peptide hormones

Peptide hormones (H) cannot enter their target cell s andmust combine with membrane receptors (R) that initi atesignal transduction processes.

KEY

TK ==== Tyrosine kinaseAE ==== Amplifier enzymeG ==== G protein

Opens ionchannel

Secondmessenger

systems

Proteins

Cellularresponse

H H

R R

G AE TK

phosphorylate

26

Hormones: Steroid

• Cholesterol-derived– Lipophilic and easily cross membranes

• Bind carrier proteins in blood– Longer half-life

• Cytoplasmic or nuclear receptors– Genomic effect to activate or repress genes for protein

synthesis– Slower acting

• Cell membrane receptors– Nongenomic responses


27 Figure 7.5a ESSENTIALS – Steroid Hormones

Cholesterol is the parent compound for all steroid hormones.

DHEA ==== dehydroepiandrosterone

==== intermediate compoundswhose names have beenomitted for simplicity.

Cholesterol

DHEA

Progesterone

Andro-stenedione

Testosterone

Dihydro-testosterone

(DHT)

Estradiol

Estrone

Ovary

Cortisol

Corticosterone Aldosterone

Adrenalcortex

Each step is catalyzed by an enzyme, but only two e nzymes are shown in this figure.

aromatase

aromatase

21-hydroxylase

21-hydroxylase

28

Figure 7.5b ESSENTIALS – Steroid Hormones

Steroid hormones act primarily on intracellular receptors.

Cell surface receptor

Rapid responses

Nucleus

DNA

Nuclearreceptor

Transcriptionproduces mRNA

TranslationNew

proteins

Endoplasmicreticulum

Cytoplasmicreceptor

Cellmembrane

Proteincarrier

Bloodvessel

Steroidhormone

Interstitialfluid

Most hydrophobic steroids are bound toplasma protein carriers. Only unboundhormones can diffuse into the target cell.

Steroid hormone receptors are in thecytoplasm or nucleus.

Some steroid hormones also bind tomembrane 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.

Translation produces new proteinsfor cell processes.

29 Figure 7.5b ESSENTIALS – Steroid Hormones

Bloodvessel


Proteincarrier

Interstitialfluid

Nucleus

Cellmembrane

Slide 1


30


Bloodvessel


Steroidhormone

Proteincarrier

Cytoplasmicreceptor

Interstitialfluid

Cellmembrane

Nucleus

Nuclearreceptor


Slide 2



Bloodvessel


Steroidhormone

Proteincarrier


Rapid responses

Cytoplasmicreceptor

Interstitialfluid

Cellmembrane

Nucleus

Nuclearreceptor


Some steroid hormones also bindto membrane receptors that usesecond messenger systems tocreate rapid cellular responses.

Slide 3


32


Bloodvessel


Steroidhormone

Proteincarrier


Rapid responses

Cytoplasmicreceptor

Interstitialfluid

Cellmembrane

Nucleus

Nuclearreceptor

DNA




Slide 4



Bloodvessel


Steroidhormone

Proteincarrier


Rapid responses

Cytoplasmicreceptor

Interstitialfluid

Cellmembrane

Translation


Nucleus

Nuclearreceptor

DNA





Slide 5


34


Bloodvessel


Steroidhormone

Proteincarrier


Rapid responses

Cytoplasmicreceptor

Endoplasmicreticulum

Interstitialfluid

Cellmembrane

Newproteins Translation


Nucleus

Nuclearreceptor

DNA




Translation produces new proteinsfor cell processes.


Slide 6


35

Hormones: Amino Acid–Derived, or Amine

• Derived from one of two amino acids– Tryptophan

– Tyrosine

• Ring structure


36

Amine Hormones: Examples

• Melatonin

• Catecholamines – Epinephrine

– Norepinephrine

– Dopamine

• Thyroid hormones


37 Figure 7.6

Most amine hormones are derived from the amino acid tyrosine.

FIGURE QUESTIONDetermine how eachcatecholamine moleculediffers from the tyrosinemolecule.

Tyrosineis the parent amino acid for

catecholamines and thyroid hormones.

Catecholaminesare made by modifying

the side groups of tyrosine.

Thyroid hormonesare synthesized from two

tyrosines and iodine (I) atoms.

Thyroxine (Tetraiodothyronine, T 4)

Triiodothyronine (T 3)Epinephrine

Norepinephrine

Dopamine

38

Biochemistry, Secretion, and Transport of Hormones


Interactive Physiology® Animation: Endocrine System: Biochemistry, Secretion, and Transport of Hormones

39

Endocrine Reflex Pathways

• Stimulus

• Sensor

• Input signal

• Integration

• Output (efferent) signal (hormone in blood)

• Targets

• Response physiological action

• Negative feedback


40

Figure 7.7a Examples of simple endocrine pathways ( 1 of 2)

Stimulus

Receptor

Hormone

Target

Tissue response

Sensory neuron

Efferent neuron

Integrating center

Systemic response

KEY

A Simple Endocrine Reflex: Parathyroid Hormone

Low plasma[Ca2+]

Parathyroidcell

Parathyroidhormone

Boneand

kidney

↑↑↑↑ Boneresorption

↑↑↑↑ Kidneyreabsorption of

calcium

Production ofcalcitriol leadsto ↑↑↑↑ intestinal

absorption of Ca 2+]

↑↑↑↑ Plasma[Ca2+]

Neg

ativ

e fe

edba

ck

41 Figure 7.7b Examples of simple endocrine pathways ( 2 of 2)

Stimulus

Receptor

Hormone

Target

Tissue response

Sensory neuron

Efferent neuron

Integrating center

Systemic response

KEY

Neg

ativ

e fe

edba

ck

↓↓↓↓ Bloodglucose

↑↑↑↑ Glucose uptakeand utilization

Targettissues

Insulin

Pancreas GLP-1

Efferent neuron

Sensoryneuron

CNS Endocrinecells in small

intestine

Glucosein lumen

Stretch receptorin digestive tract

↑↑↑↑ Bloodglucose Eat a meal

Multiple Pathways for Insulin Secretion

42

The Actions of Hormones on Target Cells


Interactive Physiology® Animation: Endocrine System: The Actions of Hormones on Target Cells

43


Introduction to the Endocrine System

Chapter 7b

44

Neurohormones: Major Groups

• Adrenal medulla – Catecholamines

• Hypothalamus– Posterior pituitary is neural tissue

– Anterior pituitary is endocrine tissue


45 Figure 7.8a ESSENTIALS – The Pituitary Gland

ANTERIOR POSTERIOR

HYPOTHALAMUS

The pituitary gland sitsin a protected pocketof bone, connected tothe brain by a thin stalk. Infundibulum is the

stalk that connectsthe pituitary to the brain.

Posterior pituitary isan extension of theneural tissue.

Anterior pituitary is atrue endocrine gland ofepithelial origin.

Sphenoid bone

46

Figure 7.8c ESSENTIALS – The Pituitary Gland

HYPOTHALAMUS

The posterior pituitary is anextension of the brain thatsecretes neurohormonesmade in the hypothalamus.

Neurohormone is madeand packaged in cellbody of neuron.

Vesicles are trans-ported down the cell.

Vesicles containingneurohormone arestored in posteriorpituitary.

Neurohormones arereleased into blood.

POSTERIOR PITUITARY

Vein

Oxytocin Vasopressin

KidneysMammary glands and uterus

Ile Gln

Tyr Asp

Cys Cys

ProLeu

GlyCys Cys

Tyr Asp

Phe Gln

ProArg

Gly

47 Figure 7.8c ESSENTIALS – The Pituitary Gland

HYPOTHALAMUS


POSTERIOR PITUITARY

Slide 1


48


HYPOTHALAMUS



POSTERIOR PITUITARY

Slide 2


49 Figure 7.8c ESSENTIALS – The Pituitary Gland

HYPOTHALAMUS




POSTERIOR PITUITARY

Slide 3


50


HYPOTHALAMUS




POSTERIOR PITUITARY

Vein

Neurohormones arereleased into blood.

Slide 4


51 Figure 7.8b ESSENTIALS – The Pituitary Gland

HYPOTHALAMUS

TO TARGET ORGANS

ProlactinGH TSH ACTH

Gonadotropins (LH & FSH)

Mammary glands Musculoskeletal system Thyroid gland Ad renal cortex

Ovary Testis

Gonads

Veins

ANTERIOR PITUITARY

Capillary bed

POSTERIOR PITUITARY

Artery

Capillary bed

Neurons synthesizingtrophic neurohormonesrelease them intocapillaries of the portalsystem.

Portal vessels carry thetrophic neurohormonesdirectly to the anteriorpituitary, where they acton the endocrine cells.

Endocrine cells releasetheir peptide hormonesinto the second set ofcapillaries for distributionto the rest of the body.

The anterior pituitary is a true endocrine gland that secretes six classichormones. Neurohormones from the hypothalamus contr ol release of theanterior pituitary hormones. The hypothalamic hormo nes reach the anteriorpituitary through a specialized region of the circu lation called a portal system.

52

Figure 7.9 ESSENTIALS – Hormones of the Hypothalamic –Anterior Pituitary Pathway 53

Endocrine Control

• A trophic hormone controls the secretion of another hormone

• Hypothalamic-hypophyseal portal system

• Three integrating centers– Hypothalamic stimulation—from CNS

– Anterior pituitary stimulation—from hypothalamic trophic hormones

– Endocrine gland stimulation—from anterior pituitary trophic hormones (except prolactin)


54

Figure 7.10

The Growth Hormone Pathway

HYPOTHALAMUS

Hypothalamic growth hormone–releasing hormone (GHRH )stimulates growth hormone (GH) secretion. Growth ho rmone actsdirectly on many body tissues but also influences l iver productionof insulin-like growth factors (IGFs or somatomedin s), anothergroup of hormones that regulate growth.

Hypothalamus

GHRH

ANTERIORPITUITARY GH cells

in anteriorpituitary

GH

Liver

IGFs

Growth

T TBone andsoft tissue

55 Figure 7.11a (1 of 2)

In complex endocrine pathways, the hormones of thepathway serve as negative feedback signals.

Stimulus

Hypothalamus(IC1)

Anteriorpituitary

(IC2)

Trophic hormone (H 1)

Trophic hormone (H 2)

Sho

rt-lo

op n

egat

ive

feed

back

Long-loop negative feedback

Endocrinegland(IC3)

Hormone (H 3)

Target tissue

Response

56

Figure 7.11b (2 of 2)

Targettissue

Response

Long-loop negative feedback

Cortisol

To targettissue

Adrenalcortex

Anteriorpituitary

ACTH

CRH

Hypothalamus

Control Pathway for Cortisol SecretionCortisol is a steroid hormone secreted by the adren al cortex.ACTH ==== corticotropin or adrenocorticotropic hormone;CRH ==== corticotropin-releasing hormone.

Draw in the short-loopnegative feedbackfor this pathway.

FIGURE QUESTION

57

Hormone Interactions

• Synergism– Combined effect is greater than the sum of individual

effects

• Permissiveness– Need second hormone to get full effect

• Antagonism– One substance opposes the action of another

– Competitive inhibitors vs. functional antagonism

– Glucagons oppose insulin


58

Figure 7.12 Synergism

Glucagon ++++ Epinephrine ++++ Cortisol

Glucagon ++++ Epinephrine

Epinephrine

GlucagonCortisol

Time (hours)

Blo

od g

luco

se (

mg/

dL)

250

200

150

100

0 1 2 3 4 5

59

Endocrine Pathologies

• Hypersecretion: excess hormone– Caused by tumors or exogenous iatrogenic treatment

– Negative feedback

• Hyposecretion: deficient hormone– Caused by decreased synthesis materials or atrophy

– Absence of negative feedback


60

Figure 7.13

↓↓↓↓CRH

↓↓↓↓ACTH

↓↓↓↓Cortisol

Response

Targettissue

Exogenouscortisol

(Hypothalamus)

(Anterior pituitary)

(Adrenal cortex)

Exogenous hormone has the same negative feedbackeffect as endogenous hormone.

61

Pathologies: Abnormal Receptors

• Down-regulation – Decreased number of receptors

– Hyperinsulinemia

• Receptor and signal transduction abnormalities– Testicular feminization syndrome

– Pseudohypothyroidism


62

Figure 7.14 Primary and secondary hypersecretion of cortisol

Secondary HypersecretionDue to Pituitary Problem

Secondary Hypersecretion Dueto Hypothalamic Problem

Primary Hypersecretion Due toProblem with Adrenal Cortex

Hypothalamus ↓↓↓↓CRH ↓↓↓↓CRH ↑↑↑↑CRH

↑↑↑↑ACTH

↑↑↑↑Cortisol↑↑↑↑Cortisol↑↑↑↑Cortisol

↑↑↑↑ACTH↓↓↓↓ACTH

Hypothalamus

Anteriorpituitary

Anteriorpituitary

Adrenalcortex

Adrenalcortex Negative

feedbackfails

PATHOLOGYIN ADRENAL

CORTEX

PATHOLOGYIN ANTERIOR

PITUITARY

HYPERSECRETINGTUMOR IN

HYPOTHALAMUS

Symptomsof excess

Symptomsof excess

Symptomsof excess

• CRH levels – low• ACTH levels – low• Cortisol levels – high

• CRH levels – low• ACTH levels – high• Cortisol levels – high

• CRH levels – high• ACTH levels – high• Cortisol levels – high

63 Figure 7.15 Patterns of hormone secretion in hypoco rtisolism

Hyposecretion from Atrophyof the Adrenal Cortex

Hyposecretion fromDamage to the Pituitary

Hypothalamus CRH Hypothalamus CRH

ACTHAnterior pituitaryACTHAnterior pituitary

CortisolAdrenal cortexCortisolAdrenal cortex

Symptomsof

deficiency

Symptomsof

deficiency

For each condition, use arrows to indicate whetherlevels of the three hormones in the pathway will beincreased, decreased, or unchanged. Draw innegative feedback loops where functional.

FIGURE QUESTION

64

The Hypothalamic-Pituitary Axis


Interactive Physiology® Animation: Endocrine System: The Hypothalamic-Pituitary Axis

65

Hormone Evolution

• Evolutionary conservation of hormone function

• Proteomics– Calcitonin gene-related peptide example

• Vestigial– Melanocyte-stimulating hormone example

• Comparative endocrinology– Pineal gland and melatonin example


66

Figure 7.16 FOCUS ON. . . – The Pineal Gland

ThalamusCorpus

callosum

The pineal gland is a pea-sized structureburied deep in the brain of humans.Nearly 2000 years ago, this “seat of thesoul” was thought to act as a valve thatregulated the flow of vital spirits andknowledge into the brain. By 1950,however, scientists had decided that itwas a vestigial structure with noknown function.

67 Figure 7.16 FOCUS ON. . . – The Pineal Gland

Melatonin is the “darkness hormone,” secreted at ni ght as wesleep. It is the chemical messenger that transmits informationabout light-dark cycles to the brain center that go verns thebody’s biological clock.

(Adapted from J. Arendt, Clin. Endocrinol. 29:205–229, 1988.)

Noon 6 P.M. Midnight 6 A.M. Noon 3 P.M.

50

40

30

20

10

0

Mel

aton

in (

pg/m

L pl

asm

a)

68

Figure 7.16 FOCUS ON. . . – The Pineal Gland

Melatonin is an amino acid–derivedhormone made from tryptophan.

69

Summary

• Hormones

• The classification of hormones

• Control of hormone release

• Hormone interactions

• Endocrine pathologies

• Hormone evolution


70

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