H ormones of adrenal cortex and adrenal medulla & S tress

1. Hormones of adrenal cortex and adrenal medulla&Stress

2. 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

3. Hormones of adrenal cortex

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

5. 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

6. 1.Effect of aldosterone: on tubular processes increases absorption of sodium and excretion of potassium total lack of aldosterone causes lossof 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+)

7. 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

8. Regulation of cortisol secretion paraventricular nuclei of hypothalamus CRH corticotrops of adenohypophysis ACTH adrenal cortex cortisol

9. adipose tissue CNS adrenals melanocytes Secretion of ACTH proopiomelanocortin b-lipotropin b-endorphin ACTH a-MSH

10. Secretion of ACTH and cortisol • ultradian rhythm (period less than 24 h) • episodic pulses • Circadian rhythm (period close to 24 h) • secretion maximumat 8-10 h • secretion minimum at 23 h

11. 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

12. 1. Effect of glucocorticoids:on carbohydrate metabolism stimulation of gluconeogenesisby the liver (rate increases 6 to 10 fold) • enzymes required to convert amino acids into glucose are increased (activation of DNA transcription) • mobilization of aminoacids from extrahepatal tissues (muscles) • increase in glycogen storage in liver cells • Decreased glucose utilization by the cells

13. 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

14. 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)

15. 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

16. Androgenic hormones • DHEA – dehydroepiandrosteron • androstendion • testosteron • testosterone is a precursor ofestradiol • effects: • anabolic • development of the secondary sexual signs • distribution of hair • voice • sexual behavior - libido

17. Excess of hormones of adrenal cortex Glucocorticoids – Cushing’s 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 Langherhans’s islets of pancreas • decreased protein synthesis in immune system - infections • osteoporosis

18. Excess of hormones of adrenal cortex Mineralocorticoids – Conn’s syndrome • hypokalemia – muscle weakness • hypervolumia – hypertension • alkalosis – increased neuromuscular excitability

19. 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 childhoodin girls and in adulthood in women • Masculinizing effect (virilizing): growth of clitoris, growth of beard, deeper voice, masculine distribution of hair

20. Lack of hormones of adrenal cortex Glucocorticoides and mineralocorticoides – Addison’s 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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22. Stress Hans Selye – nonspecific adaptation syndrome stress is the reactionof organism on external or internal factors which disturb homeostasis stressors – stimuli (factors) inducing stress distress (bad stress) vs. eustress (good stress) stress specificity

23. 3 phases of stress • alarm reaction • sympathetic-adrenomedullary system • resistance • Hypothalamic-pituitary-adrenal axis • exhaustion

24. hormonal regulation neural regulation PVN CRH Locus coeruleus noradrenaline sympathetic nervous system pituitary ACTH adrenaline cortisol preganglionic cholinergic fiber stimulation inhibition Activation of stress axis

25. 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

26. 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

27. 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