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EPINEPHRINE GLANDS

Molecular–cellular mechanisms of adrenal and sex glands hormones action. Eucosanoids: prostoglandins, tromboxans, leucotriens. EPINEPHRINE GLANDS. Two parts : - cortex - medulla. Hormones of medulla - catecholamines. Epinephrine , norepinephrine and DOPA

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EPINEPHRINE GLANDS

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  1. Molecular–cellular mechanisms of adrenal and sex glands hormones action. Eucosanoids: prostoglandins, tromboxans, leucotriens.

  2. EPINEPHRINE GLANDS Two parts: -cortex -medulla

  3. Hormones of medulla - catecholamines • Epinephrine, norepinephrine and DOPA • Nature – derivatives of tyrosine • Excretion is regulated by sympathetic nervous system and brain cortex Epinephrine Norepinephrine

  4. Stress and The Adrenal Glands

  5. Functions: Stress hormones. Contraction of vessels, increase the blood pressure, accelerate pulse. Contraction of uterus muscles. Epinephrine relaxes the muscles of bronchi and intestine. On carbohydrate metabolism: -activates the decomposition of glycogen in liver and muscles -activates glycolysis, PPC, TAC and tissue respiration On protein metabolism -accelerate the decomposition of proteins On lipid metabolism -activates lipase, mobilization of lipids and their oxidation

  6. Hormones of cortex - corticosteroids • There are more than 50 corticosteroids • Nature – steroids • Are synthesized from cholesterol • Two groups • -glucocorticoids(protein, carbohydrate and lipid metabolism) • -mineralocorticoids(mineral metabolism)

  7. Glucocorticoids Most important: corticosteron, cortison, hydrocortison Synthesis is regulated by ACTH Are transported combined with proteins Half-life time – till 1 hour In the decomposition17-ketosteroids are formed (excretion with urine). Diagnostic significance – index of the function of cortex of epinephrine glands and testis

  8. Immune system: altered Stress Circadian rhythm Hypothalamus Muscle: Net loss of amino Acids (glucose) CRH Posterior Pituitary Gland Anterior Pituitary Gland Liver: Deamination of proteins into amino acids, gluconeogenesis (glucose) (-) ACTH Adrenals Glucocorticoids, Catecholamines, etc.. Glucocorticoids, Catecholamines, etc.. Fat Cells: Free fatty acid mobilization Kidney Heart rate: Increased Hypothalamopituitary adrenal (HPA) axis: Negative Feedback

  9. Glucocorticoid Analogues

  10. Functions • Antiinflammatory, antiallergic, antiimmune • Adaptive effect • Maintain the blood pressure • Maintain the volume of extracellular liquid

  11. Effect on protein metabolism • Stimulate catabolic processes in connective, lymphoid and muscle tissues • Activate protein synthesis in liver • Stimulate amino transferases • Stimulate the urine biosynthesis

  12. Effect on the carbohydrate metabolism • Increase the glucose level • Activate gluconeogenesis • Inhibit hexokinase(glycolisis) • Effect on the lipid metabolism • Activate lipolysis • Activate the conversion of FA into carbs

  13. Mineralocorticoids The most important hormone: aldosteron Excretion is controlled byrhenin-angiothensin system Functions: -activate the reabsorption of Na, water andClinkidney canaliculi - Promotes the excretion of К ions via the kidneys, skin and saliva Aldosteron

  14. Disorders of the function of epinephrine gland cortex Insufficiency: Addison disease (bronze disease) Causes: -injury of epinephrine gland cortex -insufficient production of ACTH Blood pressure decrease, loss of weight, weakness, anorexia. Hyperpigmentation - bronze skin

  15. Hyperproduction: Kushingsyndrom Causes: hypeplasia or tumor of epinephrine gland cortex Obesity, particularly of the trunk and face (“moon face“) with sparing of the limbs; striae (stretches of the skin) Proximal muscle weakness Hirsutism (facial male-pattern hair growth) Insomnia, impotence, amenorrhoea, infertility Heart diseases, hypertension Polyuria, hypokalemia hyperglycemia, glucosuria (steroid diabetes) Kidney bones Depression, anxiety Hyperpigmentation

  16. Aldosteronehyperproduction Causes: -aldosteroma Symptoms: -hypokaliemia -hypernatriemia -hyperchloremia -hypervolemia -edema, hypertension

  17. Sex hormones Are synthesized in: -sex glands -placenta -cortex of epinephrine glands A little amount of female sex hormones is formed in male organism and vice versa. Female – estrogens, progesteron. Male – androgens.

  18. Androgens • testosterone • dehydroepiandrosterone (DHEA) • dehydroepiandrosterone sulfate (DHEAS) • androstenedione • dihydrotestosterone (DHT) • Estrogens • estradiol • estrone • estriol • Progestagens • progesterone Estradiol

  19. ACTH Cholesterol Oestriol 17-α- Hydroxy pregnenolone Dehydro-epi androsterone Pregnenolone Progesterone 17- Hydroxy progesterone Andro-stenedione Oestrone 21,βhydroxylase 11-Desoxy-corticosterone 11- Desoxy- cortisol Corticosterone 11,βhydroxylase 18-Hydroxy- corticosterone TESTOSTERONE OESTRADIOL CORTISOL ALDOSTERONE

  20. Estrogens Nature: steroids Estradiol– is formed in follicles of ovarium Estron and estriol – are formed in liver and placenta in the metabolism of estradiol estriol Estradiol

  21. Functions of estrogens Development of the female reproductive system organs Ability to fertility in reproductive period Biochemical functions of estrogens Anabolic action on the tissues of reproductive organs Inhibit the exit of Ca from bones (osteoporosis in menopause)

  22. Progesteron Nature: steroid Is formed in corpus luteum, placenta and epinephrine glands

  23. Functions of progesteron Prepares the endometrium of uterus to implantation of ovum Inhibits the uterus contraction during pregnancy Stimulates the growth of mammary glands

  24. Androgens Testosteron Nature: steroid Is formed in the interstitial cells of testis Is excreted as 17-кetosteroids

  25. Functions of testosterone Development of the primary sexfeatures Development of the secondary sexfeatures Stimulates spermatogenesis Biochemical functions of testosterone Strong anabolic action (stimulates the synthesis of NA, proteins, phospholipids) – increases the mass of muscles Keeps the Ca and P in organism

  26. Derivatives of androgens – active anabolics

  27. Major Classes of Eicosanoids • Prostaglandins • Thromboxanes • Prostacyclins • Leukotrienes

  28. Precursors of Eicosanoids • Arachidonic acid (ω6) • Eicosatrienoic acid (g-linolenic acid, ω6) • Eicosapentaenoic Acid (ω3)

  29. Prostaglandins – Structural Features

  30. PGE 9-keto reductase PGF2a PGI synthase PGI2 TXA synthase TXA2 CYCLO-OXYGENASE PATHWAY PG and TX synthesis 2GSH 2GSSG

  31. Lipoxygenase pathway

  32. Mechanism of Aspirin Action

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