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8/7/2019 Brain-Endocrine-Stress Review
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BrainBrain--EndocrineEndocrine--StressStressReviewReview
The HPA axisThe HPA axis
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HPA axisHPA axis
PVN
Anterior
Pituitary
Adrenal
Gland
Cortisol
-ve
-ve
CRF
ACTH
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CRFCRF Regulates basal and stressRegulates basal and stress--inducedinduced
release of pituitary ACTHrelease of pituitary ACTH
Detected in cerebral cortex,Detected in cerebral cortex,
hypothalamus, anterior pituitary,hypothalamus, anterior pituitary,adrenal glands, testis, ovary, gut,adrenal glands, testis, ovary, gut,heart, and lungsheart, and lungs
Three homologus neuropeptidesThree homologus neuropeptides Urcortin I, Urcortin II, and Urcortin IIIUrcortin I, Urcortin II, and Urcortin III
CRF gene expression can be alteredCRF gene expression can be altered(catecholamines, serotonin, cytokines,(catecholamines, serotonin, cytokines,
glucocorticoids)glucocorticoids)
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CRFCRF--continuedcontinued
CRF R1CRF R1
Corticotrophs of the anterior pituitaryCorticotrophs of the anterior pituitary
Mediates actions of the HPA axis andMediates actions of the HPA axis andanxietyanxiety--related behaviorrelated behavior
CRF R2CRF R2
Brain and peripheryBrain and periphery
Regulation of feeding behavior andRegulation of feeding behavior andcardiovascular functioncardiovascular function
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POMCPOMC
Proopiomelanocortin (POMC)Proopiomelanocortin (POMC)
Binding of CRF with CRF R1 onBinding of CRF with CRF R1 oncorticotrophscorticotrophs
Simulation of POMC mRNA synthesisSimulation of POMC mRNA synthesis
ACTH releaseACTH release
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Actions of glucocorticoidsActions of glucocorticoids
Two receptorsTwo receptors
Mineralocorticoid receptorsMineralocorticoid receptors
Hippocampus and sensory and motor nuclei outsideHippocampus and sensory and motor nuclei outsidethe hypothalamusthe hypothalamus
Regulation of basal expression of ACTH, CRF and AVPRegulation of basal expression of ACTH, CRF and AVP
Glucocorticoid receptorsGlucocorticoid receptors Hypothamic PVN, brainstem catecholaminergic cellHypothamic PVN, brainstem catecholaminergic cell
groups, amygdala, hippocampus, pituitarygroups, amygdala, hippocampus, pituitary
Termination of the HPA axis response to stressTermination of the HPA axis response to stress
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Actions of glucocorticoidsActions of glucocorticoids
Fetal organ maturation (esp. lungs)Fetal organ maturation (esp. lungs)
Metabolism (stimulatesMetabolism (stimulatesgluconeogenesis)gluconeogenesis)
Immune system (antiImmune system (anti--inflammatory,inflammatory,immunosuppression)immunosuppression)
Maintain vascular toneMaintain vascular tone
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Regulators of the HPARegulators of the HPA
axisaxis Cytokines (leukemiaCytokines (leukemia--inhibitory factor (LIF),inhibitory factor (LIF),
interleukininterleukin--6 (IL6 (IL--6)6)
Stimulatory on POMC gene expression and ACTHStimulatory on POMC gene expression and ACTHexpressionexpression
Vasopressin (AVP)Vasopressin (AVP)
Potentates the effects of CRF on ACTH releasePotentates the effects of CRF on ACTH release
Chronic stressChronic stress
NoradrenalineNoradrenaline
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Negative feedNegative feed--backback
Mediated by glucocorticoids at theMediated by glucocorticoids at thelevel of the pituitary andlevel of the pituitary and
hypothalamushypothalamus
Two phasesTwo phases
Rapid feedback (inhibition of CRF andRapid feedback (inhibition of CRF and
ACTH release)ACTH release) Delayed (down regulation of CRF andDelayed (down regulation of CRF and
POMC gene expression)POMC gene expression)
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Circadian rhythmicityCircadian rhythmicity
Supraoptic nucleus (SCN)Supraoptic nucleus (SCN)
Peak glucocorticoids just before activePeak glucocorticoids just before activeperiodperiod
CRF requiredCRF required
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HPA axis and stressHPA axis and stress
responseresponse Acute stressAcute stress
Systemic and neurogenicSystemic and neurogenic
Short term, enhanced secretion of ACTH andShort term, enhanced secretion of ACTH andglucocorticoidsglucocorticoids
Immunological stressImmunological stress
Stimulation by inflammatory cytokines (ILStimulation by inflammatory cytokines (IL--1, IL1, IL--
6, TNF6, TNF--EE
Repeated stressRepeated stress
Chronic stressChronic stress
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HPA axis and stressHPA axis and stress
responseresponse Repeated stressRepeated stress
HabituationHabituation
Chronic stressChronic stress
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QuestionsQuestionsFulford and Harbuz, 2005Fulford and Harbuz, 2005
1.1. What are the two systems that cause an endocrine response toWhat are the two systems that cause an endocrine response tostress?stress?
2.2. What peptides are synthesized in the parvocellular cells?What peptides are synthesized in the parvocellular cells?3.3. What are the differences between rapid and delayed feedback?What are the differences between rapid and delayed feedback?4.4. What are the 2 corticosteroid receptors and how do their functionsWhat are the 2 corticosteroid receptors and how do their functions
differ?differ?5.5. Give examples of afferent regulation of the HPA axis.Give examples of afferent regulation of the HPA axis.6.6. What are the two main categories of acute stress? GiveWhat are the two main categories of acute stress? Give
examples.examples.7.7. What effect does injecting animals with Lipopolysaccaride have onWhat effect does injecting animals with Lipopolysaccaride have on
cytokine production and on the HPA axis?cytokine production and on the HPA axis?8.8. Name some measures that can be used to evaluate an acute orName some measures that can be used to evaluate an acute or
chronic stress response.chronic stress response.9.9. How are endogenous opioids involved in the regulation of the HPAHow are endogenous opioids involved in the regulation of the HPA
axis?axis?10.10. What other factors are involved in the stress response?What other factors are involved in the stress response?
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QuestionsQuestionsAbel and Majzoub, 2005Abel and Majzoub, 2005
1.1. Describe the HPA axis.Describe the HPA axis.2.2. What is POMC?What is POMC?3.3. In what regions of the body has CRF mRNA beingIn what regions of the body has CRF mRNA being
detected?detected?4.4. What are the 2 CRF receptors and where are theyWhat are the 2 CRF receptors and where are they
distributed?distributed?5.5. What peptide is required for normal diurnal pattern of What peptide is required for normal diurnal pattern of
glucocorticoids?glucocorticoids?6.6. What is the importance of maternally derivedWhat is the importance of maternally derived
glucocorticoids?glucocorticoids?7.7. Describe an experimental design using knockDescribe an experimental design using knock--out miceout mice
to study the effects of CRF on anxiety behavior.to study the effects of CRF on anxiety behavior.