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

EPINEPHRINE GLANDS Two parts: -cortex -medulla 2

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

Stress and The Adrenal Glands

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 5

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) 6

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 9

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

Glucocorticoid Analogues

Functions Antiinflammatory, antiallergic, antiimmune Adaptive effect Maintain the blood pressure Maintain the volume of extracellular liquid 12

Corticosteroids

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 14

Effect on the carbohydrate metabolism Effect on the lipid metabolism Increase the glucose level Activate gluconeogenesis Inhibit hexokinase (glycolisis) Effect on the lipid metabolism Activate lipolysis Activate the conversion of FA into carbs 15

Mineralocorticoids Functions: The most important hormone: aldosteron Excretion is controlled by rhenin-angiothensin system Functions: -activate the reabsorption of Na, water and Cl in kidney canaliculi - Promotes the excretion of К ions via the kidneys, skin and saliva Aldosteron 16

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 17

Hyperproduction: Kushing syndrom 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 18

Aldosterone hyperproduction Causes: -aldosteroma Symptoms: -hypokaliemia -hypernatriemia -hyperchloremia -hypervolemia -edema, hypertension 19

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. 20

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

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

Estrogens Nature: steroids Estradiol – is formed in follicles of ovarium Estron and estriol – are formed in liver and placenta in the metabolism of estradiol Estradiol estriol 24

Functions of estrogens Biochemical 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) 25

Progesteron Nature: steroid Is formed in corpus luteum, placenta and epinephrine glands 26

Functions of progesteron Prepares the endometrium of uterus to implantation of ovum Inhibits the uterus contraction during pregnancy Stimulates the growth of mammary glands 27

Androgens Testosteron Nature: steroid Is formed in the interstitial cells of testis Is excreted as 17-кetosteroids 28

Functions of testosterone Biochemical functions of testosterone Development of the primary sex features Development of the secondary sex features 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 29

Derivatives of androgens – active anabolics 30

Major Classes of Eicosanoids Prostaglandins Thromboxanes Prostacyclins Leukotrienes

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

Prostaglandins – Structural Features

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

Lipoxygenase pathway

Mechanism of Aspirin Action