BrainEndocrineStress Review The HPA axis

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Brain-Endocrine-Stress Review The HPA axis
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HPA axis
PVN
-ve
CRF
Cortisol
Anterior Pituitary
-ve
ACTH
Adrenal Gland
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CRF

• Regulates basal and stress-induced release of
  pituitary ACTH
• Detected in cerebral cortex, hypothalamus,
  anterior pituitary, adrenal glands, testis,
  ovary, gut, heart, and lungs
• Three homologus neuropeptides Urcortin I,
  Urcortin II, and Urcortin III
• CRF gene expression can be altered
  (catecholamines, serotonin, cytokines,
  glucocorticoids)

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CRF-continued

• CRF R1
• Corticotrophs of the anterior pituitary
• Mediates actions of the HPA axis and
  anxiety-related behavior
• CRF R2
• Brain and periphery
• Regulation of feeding behavior and cardiovascular
  function

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POMC

• Proopiomelanocortin (POMC)
• Binding of CRF with CRF R1 on corticotrophs
• Simulation of POMC mRNA synthesis
• ACTH release

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Actions of glucocorticoids

• Two receptors
• Mineralocorticoid receptors
• Hippocampus and sensory and motor nuclei outside
  the hypothalamus
• Regulation of basal expression of ACTH, CRF and
  AVP
• Glucocorticoid receptors
• Hypothamic PVN, brainstem catecholaminergic cell
  groups, amygdala, hippocampus, pituitary
• Termination of the HPA axis response to stress

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Actions of glucocorticoids

• Fetal organ maturation (esp. lungs)
• Metabolism (stimulates gluconeogenesis)
• Immune system (anti-inflammatory,
  immunosuppression)
• Maintain vascular tone

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Regulators of the HPA axis

• Cytokines (leukemia-inhibitory factor (LIF),
  interleukin-6 (IL-6)
• Stimulatory on POMC gene expression and ACTH
  expression
• Vasopressin (AVP)
• Potentates the effects of CRF on ACTH release
• Chronic stress
• Noradrenaline

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Negative feed-back

• Mediated by glucocorticoids at the level of the
  pituitary and hypothalamus
• Two phases
• Rapid feedback (inhibition of CRF and ACTH
  release)
• Delayed (down regulation of CRF and POMC gene
  expression)

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Circadian rhythmicity

• Supraoptic nucleus (SCN)
• Peak glucocorticoids just before active period
• CRF required

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HPA axis and stress response

• Acute stress
• Systemic and neurogenic
• Short term, enhanced secretion of ACTH and
  glucocorticoids
• Immunological stress
• Stimulation by inflammatory cytokines (IL-1,
  IL-6, TNF-?
• Repeated stress
• Chronic stress

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HPA axis and stress response

• Repeated stress
• Habituation
• Chronic stress

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QuestionsFulford and Harbuz, 2005

• What are the two systems that cause an endocrine
  response to stress?
• What peptides are synthesized in the
  parvocellular cells?
• What are the differences between rapid and
  delayed feedback?
• What are the 2 corticosteroid receptors and how
  do their functions differ?
• Give examples of afferent regulation of the HPA
  axis.
• What are the two main categories of acute stress?
  Give examples.
• What effect does injecting animals with
  Lipopolysaccaride have on cytokine production and
  on the HPA axis?
• Name some measures that can be used to evaluate
  an acute or chronic stress response.
• How are endogenous opioids involved in the
  regulation of the HPA axis?
• What other factors are involved in the stress
  response?

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QuestionsAbel and Majzoub, 2005

• Describe the HPA axis.
• What is POMC?
• In what regions of the body has CRF mRNA being
  detected?
• What are the 2 CRF receptors and where are they
  distributed?
• What peptide is required for normal diurnal
  pattern of glucocorticoids?
• What is the importance of maternally derived
  glucocorticoids?
• Describe an experimental design using knock-out
  mice to study the effects of CRF on anxiety
  behavior.