Adrenal control within the

body

Presented by
Dr Tara Speranza
Department of Physiology, School of Medical Sciences
 Stress and the adrenal gland
• Recap - The HPA axis and adrenal gland anatomy:
medulla & 3 cortical layers
• Adrenal stress response
• Pharmacological actions of glucocorticoids:
immunosuppressive and anti-inflammatory
• Glucocorticoid receptor mechanism and activity
• Corticosteroid pathophysiology
• Physiological actions of mineralocorticoids:
salt and cardiovascular stress
• Chronic and acute stress responses
• Adrenal medulla and its neural connections
• Actions of adrenaline and noradrenaline
 Cortisol
The HPA pathway for the control of cortisol
secretion

Figure 23-3
 * ACTIONS OF *
Gluconeogenesis ↑ GLUCOCORTICOIDS

enzyme
synthesis ↑ LIVER
↑ GLYCEROL
FATTY ACIDS
GLUCOSE

↑AMINO ACIDS

protein  To heart &

brain
MUSCLE
ADIPOSE TISSUE
Diurnal pattern of cortisol
 Stress resistance
Physiological stress
is different from
Emotional stress

Metabolic stress Cardiovascular stress Electrolyte stress

Maintain blood Maintain blood Maintain blood Na,
glucose level pressure and flow K, Ca etc. levels

Adrenaline Adrenaline, Aldosterone,

Cortisol Angiotensin, ADH, Angiotensin,
Glucagon Cortisol, Parathyroid hormone,
Growth hormone Thyroid hormone Vitamin D
 Stress resistance
Vascular reactivity
Cortisol induces ↑ responsiveness of blood vessels
to catecholamines, angiotensin, etc i.e. “permissive
effect” for vasoconstriction – eg upregulate
expression of alpha 1B adrenergic receptor in
vascular smooth muscle: Sakaue and Hoffman, JCI
1991
 Clinical Use of Glucocorticoids
Rheumatoid arthritis Colitis Bullous pemphigoid

Lupus erythematosus Asthma Transplantation

 Effects – Desired & Adverse
Clinical Effects

Anti-allergic
Anti- Pain Relief
Inflammatory (secondary)

Effects on cells, tissues & GOOD

organs
Immuno-
Permeability
suppression Immune Cells
Vessels

Infections
GCs Cardio-
Muscle Eyes vascular
Atrophy Bone CNS Skin Cataract,
Metabolism glaucoma
HPA axis BAD
Osteoporosis,
osteonecrosis Weight gain/obesity, Skin thinning
oedema, Cushingoid
Neuropsychiatri appearance, glucose
c, HPA intolerance, Diabetes
insufficiency
Buttgereit et al. 2005
 Glucocorticoid Action in The Cell
GCs bind to the cognate intracellular GC receptor (GR).

GCs GR
GR
GR

jun
fos p50
p65
Glucocorticoid Action in The Cell
Translocation of the GC-GR complex to the nucleus
Differentiation 
Apoptosis 
GR IL-1, IL-6, TNFa 
GR Phospholipase A2 
GR COX 2 

jun
fos p50
p65

Activation or transcription of hormone sensitive genes

Interaction with transcriptional regulators (e.g. NFkB, fos-jun)
 Corticosteroid pathophysiology
1. Cushing’s syndrome due to Cortisol Excess:
produces symptoms of moon face, abdominal
fat, thin legs, bruising, insulin resistance and
hyperglycemia, hypertension, osteoporosis
May occur with long-term steroid treatment
2. Addison’s disease due to Cortisol and
Aldosterone Deficiency:
produces symptoms of hypoglycemia,
hypotension, skin pigmentation
3. Conn’s syndrome due to Aldosterone Excess:
produces symptoms of excess Na and water
retention and K loss= poor vision, confusion
or headaches
The Four Mechanisms of Aldosterone Secretion

Figure 16.13
Figure 20-13
Stress and the Adrenal Gland

Figure 16.15
Adrenal Medulla

Figure 11-10c
Table 22-4
Summary of stress response of adrenal
hormones
• Chronic stress • Acute stress:
• Adrenal cortex • Adrenal medulla
• Salt,Sugar,Sex,Stress • Fright/fight or flight
• Salt: mineralocorticoid • Adrenaline & NorAdr
aldosterone (mainly fr. Sympathetic)
• Sugar: glucocorticoid • Equal on β1 in heart
cortisol SA node & ventricles
• Sex: mainly androgen • Adr ≥Nor on β2 in
important at certain blood vessel smooth
times, especially during muscle, & bronchioles
childhood and • Adr ≤ Nor on α in BV
adolecence
 Summary of metabolic actions
Adrenaline & Glucagon
• Both stimulate gluconeo-
genesis mainly in liver
• Both stimulate
glycogenolysis, glucagon
mainly in liver
• Muscle glycogen not able
to release glucose into
blood as no phosphatase
• Both stimulate lipolysis
• Glucagon stimulates
ketogenesis in liver
• Neither stimulates protein
breakdown
Cortisol & Growth hormone
• Both stimulate gluconeo-
genesis
• Both stimulate lipolysis
• Cortisol stimulates protein
breakdown in muscle but
enzyme synthesis in liver
• Cortisol stimulates
glycogen synthesis in liver
• Growth hormone
stimulates protein
synthesis
• Both decrease glucose
uptake in muscle and fat
Learning Outcomes
• Recap - The HPA axis and adrenal gland anatomy:
medulla & 3 cortical layers
• Adrenal stress response
• Pharmacological actions of glucocorticoids:
immunosuppressive and anti-inflammatory
• Glucocorticoid receptor mechanism and activity
• Corticosteroid pathophysiology
• Physiological actions of mineralocorticoids:
salt and cardiovascular stress
• Chronic and acute stress responses
• Adrenal medulla and its neural connections
• Actions of adrenaline and noradrenaline