29.11.19
L8 – Chronic stress axis (Hypothalamic-pituitary-adrenocortical axis)
Keywords:
Stress (a process initiated by evens that threaten, harm or
challenge an organism)
Lecture:
Anterior pituitary (mostly all proteins)
o Adrenocorticotropin = peptide
HPA axis
o Secretion of CRH or AVP in hypothalamus
o Stimulates adrenocorticotrophic hormone
(ACTH)
ACTH = peptide hormone in family of
melanocortin all from POMC
precursor
Zona fasciculata (cortisol secretion via ACTH)
o Cholesterol – rate limiting via ACTH moving
from cytoplasm to mitochondria→
pregnenolone
o 5 minutes between stimulation and
cholesterol
o Thickened zona with increased stress
Constant circadian rhythm (max between 6-8am and fall)
Reversed rhythm in nocturnal
Cortisol (steroid)
o Hydrophobic (80% use binding protein – transcortin (liver))
o Stimulates glucose synthesis (gluconeogenesis – make from FA/proteins)
Stimulates lipolysis to increase FA production
Stimulates muscle breakdown (get AAs for glycogenesis)
o Stored as glycogen
o Stimulates appetite
o Anti-inflammatory (immunosuppression to ↓ neutrophils)
Using glucocorticoids for immunosuppressants/arteritis
Down reg for ACTH axis (- feedback)
Disfunction of the HPA axis (Cushing’s)
o SYNDROME = Cortisol over-production (side-effect of steroid medication)
Use of glucocorticoids
o DISEASE = Natural cause = tumor in pit (synth ACTH/CRH (less common))
Ectopic = tumor producing ACTH in ling
Adrenal tumor = direct cortisol synth
o Symptoms
Central obesity
Thinning of the skin
Bruising (burst caps)
Hypertension
Bone and muscle wasting
, 29.11.19
o Diagnosis
Cortisol presence in the urine
Rarely measure ACTH in blood bc unstable
If adrenal tumor = low levels of ACTH
Ectopic tumor = high levels of ACTH ]
Pituitary tumor = middle
Dexamethasone (glucocorticoid)
Normal person = suppress ACTH
Pit tumor = not suppressing
Petrosal sinus fluid
Take blood samples (high levels of ACTH)
o Treatment
Steroids (reduce glucocorticoid given – slow reduction as adrenals would not
synth cortisol independently)
Pit tumor = remove surgically
Transnasal approach (via nose)
Adrenalectomy
Remove adrenals (easier)
Low cortisol levels so large ACTH levels
o Nelson’s syndrome = can get pigmentation change
L8 – Chronic stress axis (Hypothalamic-pituitary-adrenocortical axis)
Keywords:
Stress (a process initiated by evens that threaten, harm or
challenge an organism)
Lecture:
Anterior pituitary (mostly all proteins)
o Adrenocorticotropin = peptide
HPA axis
o Secretion of CRH or AVP in hypothalamus
o Stimulates adrenocorticotrophic hormone
(ACTH)
ACTH = peptide hormone in family of
melanocortin all from POMC
precursor
Zona fasciculata (cortisol secretion via ACTH)
o Cholesterol – rate limiting via ACTH moving
from cytoplasm to mitochondria→
pregnenolone
o 5 minutes between stimulation and
cholesterol
o Thickened zona with increased stress
Constant circadian rhythm (max between 6-8am and fall)
Reversed rhythm in nocturnal
Cortisol (steroid)
o Hydrophobic (80% use binding protein – transcortin (liver))
o Stimulates glucose synthesis (gluconeogenesis – make from FA/proteins)
Stimulates lipolysis to increase FA production
Stimulates muscle breakdown (get AAs for glycogenesis)
o Stored as glycogen
o Stimulates appetite
o Anti-inflammatory (immunosuppression to ↓ neutrophils)
Using glucocorticoids for immunosuppressants/arteritis
Down reg for ACTH axis (- feedback)
Disfunction of the HPA axis (Cushing’s)
o SYNDROME = Cortisol over-production (side-effect of steroid medication)
Use of glucocorticoids
o DISEASE = Natural cause = tumor in pit (synth ACTH/CRH (less common))
Ectopic = tumor producing ACTH in ling
Adrenal tumor = direct cortisol synth
o Symptoms
Central obesity
Thinning of the skin
Bruising (burst caps)
Hypertension
Bone and muscle wasting
, 29.11.19
o Diagnosis
Cortisol presence in the urine
Rarely measure ACTH in blood bc unstable
If adrenal tumor = low levels of ACTH
Ectopic tumor = high levels of ACTH ]
Pituitary tumor = middle
Dexamethasone (glucocorticoid)
Normal person = suppress ACTH
Pit tumor = not suppressing
Petrosal sinus fluid
Take blood samples (high levels of ACTH)
o Treatment
Steroids (reduce glucocorticoid given – slow reduction as adrenals would not
synth cortisol independently)
Pit tumor = remove surgically
Transnasal approach (via nose)
Adrenalectomy
Remove adrenals (easier)
Low cortisol levels so large ACTH levels
o Nelson’s syndrome = can get pigmentation change
