Hormones of adrenal cortex and adrenal medulla & Stress

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Hormones of adrenal cortex and adrenal
medullaStress
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Adrenal glands

• weight 4-5 g
• Cortex - 80 synthesis of steroid hormones
• zona glomerulosa - mineralocorticoids
• zona fasciculata glukocorticoids
• zona reticularis adrenal androgens
• centripetal blood flow gradient of steroid
  hormones
• enzymes
• Medulla - 20 synthesis of noradrenaline and
  adrenaline
• Functionally a part of sympathetic nervous system

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Hormones of adrenal cortex

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Regulation of aldosterone secretion

• hypovolemia, (decrease of natremia)
• decrease of renal perfusion pressure
• renin secretion by juxtaglomerular apparatus
• conversion of angiotenzinogen to angiotenzin I
• conversion ofr angiotenzin I to angiotenzin II
• stimulation of aldosterone production

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Transport of aldosterone in the blood

• 50 bound to plasma proteins
• 50 free
• effect of aldosterone after 30 min
• circulating half-life 15 minut
• Most aldosterone is metabolically inactivated
  during a single passage through the liver

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1. Effect of aldosterone on tubular processes

• increases absorption of sodium and excretion of
  potassium
• total lack of aldosterone causes loss of 20 g Na
  / day
• increased secretion of aldosterone
• hypokalemia decrease from 4.5 mmol/l (norm) to
  1 - 2 mmol/l (muscle weakness)
• alkalosis (increased excretion of H)
• decreased secretion of aldosterone
• increase plasma K 60 - 100 above normal level -
  hyperkalemia (cardiac toxicity)
• acidosis (decreased excretion of H)

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Other effects of mineralocorticoides

• 2) on extracellular fluid volume
• increase of ECF - absorption of Na is followed
  by osmotic absorption of water,
• therefore Na concentration in ECF is not changed
• 3) on blood pressure
• increase in ECF volume leads to an increase in
  arterial pressure
• 4) on sweat glands, salivary glands, intestinal
  absorption

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Regulation of cortisol secretion
paraventricular nuclei of hypothalamus
CRH
corticotrops of adenohypophysis
ACTH
adrenal cortex
cortisol
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Secretion of ACTH
proopiomelanocortin
b-lipotropin
b-endorphin
ACTH
a-MSH
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Secretion of ACTH and cortisol

• ultradian rhythm (period less than 24 h)
• episodic pulses
• Circadian rhythm (period close to 24 h)
• secretion maximum at 8-10 h
• secretion minimum at 23 h

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Transport of cortisol in the blood

• 90 bound to CBP (corticosteroid binding protein
  cortisol binding globulin transcortin)
• 4 bound to albumin
• 6 free
• the effect of cortisol after 1-2 hours
• circulating half-life 90 minutes

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1. Effect of glucocorticoids on carbohydrate
metabolism

• stimulation of gluconeogenesis by the liver (rate
  increases 6 to 10 fold)
• enzymes required to convert amino acids into
  glucose are increased (activation of DNA
  transcription)
• mobilization of amino acids from extrahepatal
  tissues (muscles)
• increase in glycogen storage in liver cells
• Decreased glucose utilization by the cells

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2. Effect of glucocorticoids on protein
metabolism

• mobilization of amino acids from non-hepatic
  tissues
• proteokatabolic effect in all body cells except
  of the liver
• decreased protein synthesis
• decreased amino acids transport into extrahepatic
  tissues (muscles, lymphatic tissues)
• Proteoanabolic effect in the liver
• enhanced liver proteins
• increased plasma proteins

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3. Effect of glucocorticoids on fat metabolism

• mobilization of fatty acids from adipose tissue
• moderately enhance the oxidation of fatty acids
  (lower glucose utilization stimulates the cells
  to utilize energy from fatty acids)

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4. Effect of glucocorticoids anti-inflammatory
effect

• release from damage tissues proteolytic enzymes,
  histamine, bradykinin
• cortisol stabilizes lysosomal membrane
• increase the blood flow in inflamed area -
  vasodilatation
• cortisol reduces degree of vasodilatation
• leakage of plasma into damage area - clotting
• cortisol decreases permeability of capillaries,
  prevents loss of plasma
• infiltration by leukocytes
• cortisol decreases migration of white blood cells
• suppresses immune system reduction of
  T-lymphocyte

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Androgenic hormones

• DHEA dehydroepiandrosteron
• androstendion
• testosteron
• testosterone is a precursor of estradiol
• effects
• anabolic
• development of the secondary sexual signs
• distribution of hair
• voice
• sexual behavior - libido

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Excess of hormones of adrenal cortex

• Glucocorticoids Cushings syndrome (diessease)
• redistribution of body fat deposition to
  thoracic and upper abdominal region buffalo
  torzo, moon face
• hypertension
• steroid (adrenal) diabetes increased glucose
  concentration burn-out of Langherhanss
  islets of pancreas
• decreased protein synthesis in immune system -
  infections
• osteoporosis

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Excess of hormones of adrenal cortex

• Mineralocorticoids Conns syndrome
• hypokalemia muscle weakness
• hypervolumia hypertension
• alkalosis increased neuromuscular excitability

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Excess of hormones of adrenal cortex

• Andogenic hormones
• in childhood in boys
• pseudopubertas praecox rapid development of male
  sexual organs
• in adulthood in men non-visible
• in childhood in girls and in adulthood in women
• Masculinizing effect (virilizing) growth of
  clitoris, growth of beard, deeper voice,
  masculine distribution of hair

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Lack of hormones of adrenal cortex

• Glucocorticoides and mineralocorticoides
  Addisons dissease
• consequences of lack of aldosterone
• decreased Na reabsorption, decreased ECF volume
• hypercalemia, mild acidosis
• rise of hematocrit decrease of cardiac output
• consequences of lack of cortisol
• depressed gluconeogenesis
• reduced fat and protein metabolism
• high level of ACTH - pigmentation
• Addisonian crisis - during stress (trauma,
  surgical operations) extra need for
  glucocorticoids

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Stroops test
red blue green blue green red blue red blue green
blue red blue green red green red blue red blue
red green red blue red blue green blue green red
blue red blue green blue red blue green red green
red blue red blue red green red blue red blue
green blue green red blue red blue green blue red
blue green red green red blue red blue red green
red blue red blue green blue green red blue
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Stress

• Hans Selye nonspecific adaptation syndrome
• stress is the reaction of organism on external or
  internal factors which disturb homeostasis
• stressors stimuli (factors) inducing stress
• distress (bad stress) vs. eustress (good stress)
• stress specificity

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3 phases of stress

• alarm reaction
• sympathetic-adrenomedullary system
• resistance
• Hypothalamic-pituitary-adrenal axis
• exhaustion

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Activation of stress axis
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Hormones of adrenal medulla

• noradrenaline 20 1.2 - 3.4 nmol/l
• 5 - 6 fold increase exerts biological action
• adrenaline 80 0.1 - 0.8 nmol/l
• 2 fold increase can elicit physiological response

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Effect of catecholamines during stress

• Alarm reaction - immediate
• 1) increased hepatic and muscle glycogenolysis
• 2) increased breakdown of adipose tissue -
  lipolysis
• 3) blockade of insulin
• 4) increased cardiac output (increased
  contractility, heart rate)
• 5) shunting blood from visceral to skeletal
  muscles by means of vasoconstriction in visceral
  and vasodilatation in skeletal
• 6) increased ventilation
• 7) decreased fatigue of skeletal muscle
• 8) Increased coagulability of blood

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Effect of cortisol during stress

• Effect of cortisol after 2 - 4 hours
• inhibits glucose uptake by many cells
• stimulates gluconeogenesis
• stimulates protein catabolism
• vascular effect sensibilization of vessels to
  the effect of noradrenaline - vasocontsriction
• 5) Effect on memory ACTH facilitates learning
  an dmemory in experimental animals helps to
  cope with the stress
• however, long-lasting stress impairs learning
• cortisol damages neurons in hippocampus