Adrenal Glands

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• Adrenal Glands

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Endocrine glands
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Adrenal gland
3 cm

Adrenal cortex (corticosteroids)
Adrenal medulla (catecholamine - adrenaline)
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Catecholamines

• 3 major catecholamines
• dopamine, noradrenaline - neurotransmitters
• adrenaline (epinephrine) hormone (adrenal
  medulla)
• All derived from tyrosine single pathway
• tyrosine ? dopa ? dopamine ? noradrenaline ?
  adrenaline

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Adrenaline

• OH
• HO CH(OH)-CH2-NH(CH3)

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Actions of adrenaline

• Part of the rapid response to stress fight or
  flight response.
• Metabolic actions
• Mobilises fuel reserves (catabolic)
• ? glycogenolysis lipolysis
• ? insulin secretion
• Actions on respiratory system
• bronchodilatation increases O2 supply removal
  of CO2 .
• Actions on cardiovascular system (CVS)
• ? rate force of contraction of heart - ?
  cardiac output.
• diverts blood away from skin gut
  (vasoconstriction) to muscle (vasodilatation).

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Actions of adrenaline

• Net effect
• Prepares body for activity of skeletal muscle
  (fight or flight).
• Increased availability of nutrients (glucose
  fatty acids).
• Increased blood supply to muscle
• brings nutrients oxygen.
• takes away waste products.

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Adrenal cortex

• zona glomerulosa
• mineralocorticoids
• zona fasiculata
• glucocorticoids
• zona reticularis
• androgens

adrenal cortex (corticosteroids)
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Corticosteroid synthesis

• cholesterol ester
• cholesterol (C27)
• progesterone (C21)
• mineralocorticoids (C21) glucocorticoids
  (C21)
• (aldosterone) (cortisol)
• androgens (C19)
• (testosterone)

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Control of adrenal gland

• releasing hormone
• trophic hormone
• cortisol

hypothalamus
-
anterior pituitary
-
adrenal
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Hypothalamic releasing hormones affecting
anterior pituitary
Hypothalamus (Releasing Hormone) Corticotrophin
RH (CRH) Gonadotrophin RH (GnRH) Somatotrophin
RH
Anterior Pituitary (Trophic Hormone) Corticotroph
in (ACTH) Adrenocorticotrophic Hormone Luteinizin
g hormone (LH) Follicle-Stimulating Hormone
(FSH) Somatotrophin (Growth Hormone)
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Control of adrenal gland

• -
• CRH (41 amino acids)
• -
• ACTH
• cortisol

hypothalamus
anterior pituitary
adrenal
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Factors affecting CRH release from hypothalamus

• Stress
• hypoglycaemia
• infection
• exercise
• cold exposure
• emotional activity
• Shock (state of inadequate tissue perfusion)
• haemorrhage
• burns
• trauma

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Control of adrenal gland

• -
• CRH
• -
• ACTH (39 amino acids)
• cortisol

hypothalamus
anterior pituitary
adrenal
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ACTH synthesis in pituitary

• Synthesized as large protein hormone precursor
  (250 amino acids) Pro-opiomelanocortin (POMC)
• Post-translational processing to produce a
  variety of products
• ACTH
• ?-endorphin (morphine-like actions)
• ACTH contains amino acid sequence of MSH
  (melanocyte stimulating hormone).
• ACTH interacts with receptors on surface of cells
  in adrenal cortex (zona fasiculata).

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Transport of cortisol

• cortisol

adrenal
blood
Bound (90)
free
target tissues
response inactivation
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Mechanism of cortisol action
C
Plasma membrane
R
C
nucleus
R
C
DNA
protein synthesis
mRNA
Response
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Steroid hormone receptors

• All have similar basic structure 3 regions
  (domains)
• Sequence homology in steroid binding region
• homology with glucocorticoid receptor
• mineralocorticoid receptor 64
• androgen receptor 66
• oestrogen receptor 31
• T3 receptor 23

variable region DNA binding region
steroid binding region
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Inactivation of cortisol

• Liver is major tissue
• Small change in structure
• introduction of hydroxyl group in position 17
• produces 17-hydroxysteroids
• Inactivates and increases water solubility.
• Excreted via kidneys in urine (some cortisol
  excreted unchanged).
• Measure amount of 17-hydroxysteroids/cortisol in
  a 24hr urine collection test for excess
  cortisol secretion.

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Major actions of cortisol

• Part of the normal response to prolonged stress
• Metabolic actions maintains blood glucose.
• Suppresses bodys defence mechanisms.
• Metabolic actions (anti-insulin)
• adipose tissue - stimulates lipolysis.
• N.B. Excess stimulates lipogenesis in face,
  neck trunk.
• muscle - stimulates proteolysis.
• liver - stimulates gluconeogenesis.
• Net effect raises blood glucose
• Excess cortisol steroid-induced diabetes

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Major actions of cortisol

• Suppression of bodys defence mechanisms
• anti-inflammatory.
• immunosuppressive.
• anti-allergic.
• Used pharmacologically - asthma, arthritis,
  allergy, transplantation.
• Mineralocorticoid effects
• increases Na water retention.

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Overview of actions of cortisol

• Major component of response to prolonged stress
  (trauma, infection) takes over from sympathetic
  nervous system.
• Maintains blood nutrient levels tissue fuel
  supplies maintained.
• Reduce inflammatory immune response
• reduces pain, decreases immobilization.
• reduces awareness of severity of situation.
• allows individual to perform despite the injury
  or infection (steroid injections in sports
  injuries)

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Adrenal cortex pathophysiology

• Over-secretion or under-secretion of cortisol.
• Too much cortisol
• Cushings syndrome
• Not enough cortisol
• Addisons disease
• Pituitary problem (ACTH?)
• Adrenal problem (ACTH ?, also affects
  mineralocorticoids)
• Congenital adrenal hyperplasia

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Signs and symptoms of Cushings Syndrome

• Immunosuppressive actions - increased
  susceptibility to infection (acne).
• Action on bone - osteoporosis (pain rib
  collapse).
• Hypertension (mineralocorticoid effect of
  cortisol).

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Signs symptoms of Addisons Disease

• tiredness, weakness, weight loss, anorexia.
• fasting hypoglycaemia.
• ACTH induced pigmentation (MSH actions of ACTH).
• may be postural hypotension (dehydration
  sodium depletion lack of mineralocorticoid).

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