6.Adrenal galnds.ppt

1. Hormones of the Adrenal Glands 31-May-23 Adrenal Medulla Hormones 1

2. Adrenal Glands • Suprarenal glands • Divided into – outer Cortex and inner Medulla 31-May-23 Adrenal Medulla Hormones 2

3. Adrenal Glands • Suprarenal glands weigh 5 gm • Divided into outer Cortex (80% of gland) and inner Medulla (20% of gland) • Despite their organization – into a single gland, the medulla and cortex are functionally different endocrine organs, and have different embryological origins. • The medulla – is derived from ectoderm (neural crest), – while the cortex develops from mesoderm. 31-May-23 Adrenal Medulla Hormones 3

4. Adrenal Medulla 31-May-23 Adrenal Medulla Hormones 4

5. Adrenal Medulla • Cells in the adrenal medulla – synthesize and secrete catecholamine • norepinephrine, epinephrine & dopamine – also small amount of opioid peptides • met-enkephalin, leu-enkephalin • Roughly 80% of the catecholamine output is epinephrine 31-May-23 Adrenal Medulla Hormones 5

6. Adrenal Medulla  In adrenal medulla  The chromaffin cell is the principle cell type.  There are epinephrine releasing chromaffin cells and norepinephrine releasing cells 31-May-23 Adrenal Medulla Hormones 6

7. Adrenal Medulla • 80% of chromaffin cells – secrete adrenalin – 20% secrete nor adrenalin  The medulla is richly innervated  by preganglionic sympathetic fibers  and is, in essence, an extension of the sympathetic nervous system. 31-May-23 Adrenal Medulla Hormones 7

8. Adrenal Medulla • The chromaffin cells – are like the post ganglionic cells – in the sympathetic nervous system • The pre-ganglionic fibres – Originate from T5 – T9 31-May-23 Adrenal Medulla Hormones 8 T5 – T9 Symp preganglionic nerve Chromaffin cells Adrenalin Noradrenalin

9. Adrenal Medulla • These preganglionic fibres – release acetylcholine as the neurotransmitter • Ach cause the chromaffin cells to release – Adrenalin – Nor-adrenalin 31-May-23 Adrenal Medulla Hormones 9 T5 – T9 Symp preganglionic nerve Chromaffin cells Adrenalin Noradrenalin Ach

10. Adrenal Medulla • Adrenalin – Mainly produced in adrenal medulla – Small amount is secreted in brain • Nor adrenalin – Widely distributed in neural tissues including • Adrenal medulla • Sympathetic postganglionic fibers • CNS 31-May-23 Adrenal Medulla Hormones 10

11. Biosynthesis of Catecholamines 31-May-23 Adrenal Medulla Hormones 11 Phenylalanine Tyrosine Dihydroxy-phenylalanine (DOPA) Dihydroxy-phenyl-ethylamine (DOPAMINE) Nor-epinephrine Epinephrine Phenylalanine hydroxylase Tyrosine hydroxylase Dopa decarboxylase Dopa  hydroxylase Phenylethanolamine-N- methyltransferase

12. Control of Secretion • Secretion of catecholamine – by chromaffin cells is stimulated by • Acetylcholine • Angiotensin II • Histamine • Bradykinin 31-May-23 Adrenal Medulla Hormones 12

13. Control of Secretion • Stress – Flight or fight reaction – Activation of sympathetic system • Fear, anxiety, pain, trauma, hemorrhage • Any stressful situation – Lead to release of catecholamines 31-May-23 Adrenal Medulla Hormones 13

14. Physiological Actions • In general, – circulating epinephrine&norepinephrine – released from the adrenal medulla – have the same effects on target organs as direct stimulation by sympathetic nerves. 31-May-23 Adrenal Medulla Hormones 14

15. Physiological Actions • Complex physiologic responses – result from adrenal medullary stimulation – because there are multiple receptor types – which are differentially expressed – in different tissues and cells 31-May-23 Adrenal Medulla Hormones 15

16. Physiological Actions • Effects depend on the type of receptors on target organ – receptors or  receptors • Adrenaline act on both  and  receptors • Nor adrenaline act mainly on  receptors 31-May-23 Adrenal Medulla Hormones 16

17. Physiological Actions •  Adrenergic receptors – Associated with excitatory function of the body – Associated with inhibitory functions of intestinal motility •  Adrenergic receptors – Associated with most of inhibitory functions of the body • Except on the myocardium –Excitation • 31-May-23 Adrenal Medulla Hormones 17

18. Physiological Actions • Effects on the heart –Nor-adrenalin & adrenalin both increase the • Heart rate, force of contraction (1 receptors) –Increase effectiveness of the heart • Myocardial excitability 31-May-23 Adrenal Medulla Hormones 18

19. Physiological Actions • On blood vessels –Vasoconstriction (1 receptors) • Adrenalin causes –Vasodilatation (liver, skeletal muscle) • 2 receptors 31-May-23 Adrenal Medulla Hormones 19

20. Physiological Actions • Adrenalin & nor-adrenalin exert metabolic effect –Glycogenolysis –Mobilization of FFA –Stimulate metabolic rate 31-May-23 Adrenal Medulla Hormones 20

21. Questions?

22. Hormones of the Adrenal cortex 31-May-23 Adrenocortical Hormones 22

23. Adrenal Cortex • Synthesize and secrete – steroid hormones (corticosteroids) • Synthesize from steroid cholesterol • Have nearly similar chemical formula • Slight differences in molecular structure give them different functions 31-May-23 Adrenocortical Hormones 23

24. Corticosteroids • Three groups of corticosteroids • Mineralocorticoids – Effect on electrolytes • Glucocorticoids – Exhibit important effect in increasing blood glucose concentration – Also affect fat, protein metabolism • Androgens – Sex hormones 31-May-23 Adrenocortical Hormones 24

25. Adrenal Cortex • Histologic examination – of the cortex reveals – three concentric zones of cells – that differ in the major steroid hormones – they secrete 31-May-23 Adrenocortical Hormones 25 Glomerulosa Fasciculata Reticularis Medulla

26. Adrenal Cortex • Zona glomerulosa – Secrete aldosterone • Have aldosterone synthase 31-May-23 Adrenocortical Hormones 26 Glomerulosa Fasciculata Reticularis Medulla

27. Adrenal Cortex • Zona fasciculata – middle layer of cortex • Zona reticularis – Innermost layer of cortex • Zona fasciculata & reticularis – Secrete cortisol & androgens 31-May-23 Adrenocortical Hormones 27 Glomerulosa Fasciculata Reticularis Medulla

28. Structure of steroid hormones • All steroids – have the same basic cyclopentanoperh ydrophenanthrene ring structure • Have – 3 cyclohexyl rings • ( A, B, C) – One cyclopentyl ring (D) 31-May-23 Adrenocortical Hormones 28 19 3 2 1 8 7 6 5 4 10 9 15 14 13 12 11 18 17 16 A B C D Cyclopentanoperhydrophenanthrene

29. 31-May-23 Adrenocortical Hormones 29

30. Transport & Fate of Adrenal Hormones • Cortisol – Combine with Cortisol binding globulin (CBG) • Transcortin • Also can combine with albumin • About 94% transported in bound form; 6% in free form 31-May-23 Adrenocortical Hormones 30

31. Transport & Fate of Adrenal Hormones • Aldosterone –Combine loosely with plasma protein –About 50% is in free form • Both combined and free forms –are transported through out ECF 31-May-23 Adrenocortical Hormones 31

32. Transport & Fate of Adrenal Hormones • Adrenal steroids degraded in liver • Conjugated to glucoronides or sulfated to sulfate – Then 25% excreted though bile – 75% excreted through urine • Hence diseases of liver – Greatly affect hormone degradation 31-May-23 Adrenocortical Hormones 32

33. Glucocorticoids 31-May-23 Adrenocortical Hormones 33

34. Functions of Glucocorticoids • Affect metabolic systems for utilizing – Carbohydrates – Proteins – Fats • 95% of glucocorticoid activity – of adrenal cortex – result from Cortisol 31-May-23 Adrenocortical Hormones 34

35. Mechanism of Action • Multiple effects – of glucocorticoids – triggered by – binding to intracellular receptors – which interact with specific regulatory DNA sequences • Glucocorticoids Response Element 31-May-23 Adrenocortical Hormones 35

36. Mechanism of Action • Induce or repress – gene transcription • Leads to increased or decreased – formation of mRNA • Alters synthesis of enzymes • Alter cell functions 31-May-23 Adrenocortical Hormones 36

37. Effects of Cortisol on carbohydrate metabolism • Stimulate gluconeogenesis – liver enzymes for converting AA into glucose •  glucose utilization by cells – Exert anti insulin effect • Block glucose transport in muscle & adipose tissue • Cortisol indirectly inhibit activity of glycolytic enzymes • Glucokinase, phosphofructokinase, pyruvate kinase 31-May-23 Adrenocortical Hormones 37

38. Effects of Cortisol on Protein Metabolism • Glucocorticoids enhance protein catabolism in skeletal muscle, and other extra hepatic tissues • Released AA are transported to liver where are converted to glucose • Glucocorticoids inhibit protein synthesis 31-May-23 Adrenocortical Hormones 38

39. Effects of Cortisol on Fat Metabolism • Glucocorticoids are lipolytic – Potentiate lipolytic actions of other hormones • GH, catecholamines, glucagon, T3,T4 – Favour FA mobilization • from adipose tissue to liver 31-May-23 Adrenocortical Hormones 39

40. Fat Metabolism • FFA metabolized by liver – -Oxidation • formation of ketone bodies – Inhibit glycolysis • Fructose 1,6 diphosphatase – Activated by FA • Pyruvate kinase , phosphofructokinase – Inhibited by FA • Glycolysis is inhibited, gluconeogenesis proceeds 31-May-23 Adrenocortical Hormones 40

41. Fat Metabolism • Glucocorticoids indirectly stimulate lipolysis by – Blocking peripheral glucose uptake, utilization – Inhibit re-esterification of FA in adipose tissue • Inhibit the use of glucose 31-May-23 Adrenocortical Hormones 41

42. Effects of Cortisol on Fat Metabolism • Cortisol inhibit FA synthesis in the liver – This effect is not observed in adipose tissue • Overall effect – Redistribution of body fat –  In total body fat • Truncal obesity 31-May-23 Adrenocortical Hormones 42

43. Effects of Cortisol on Fat Metabolism • Characteristic centripetal distribution of fat – Accumulation of fat on central axis of body – Deposition of fat on the face • Moon face 31-May-23 Adrenocortical Hormones 43

44. Effects of Cortisol on Fat Metabolism • Deposition of fat in supra scapular region • Buffalo hump – Excessive fat distribution • Pendulous abdomen 31-May-23 Adrenocortical Hormones 44

45. Anti-inflammatory and immunosuppressive effects • The anti-inflammatory and immunosuppressive effects – of glucocorticoids are largely secondary to their inhibition of the immune responses • of lymphocytes, macrophages, and fibroblasts. • Also by stabilizing the lysosomes – of damaged cells – preventing the release of the mediators of inflammation 31-May-23 Adrenocortical Hormones 45

46. anti-inflammatory and immunosuppressive effects • Whereas NSAIDs principally – inhibit prostaglandin synthesis, – corticosteroids interfere earlier – in the inflammatory cascade – by inhibiting PLA2 actions – and thereby curtailing • both the leukotriene and prostaglandin mediated inflammatory response 31-May-23 Adrenocortical Hormones 46

47. anti-inflammatory and immunosuppressive effects • increased levels of glucocorticoids – serve to suppress the immune system. • This is achieved by decreasing – the production of lymphocytes (especially T cells) and antibodies – Also reduce number of eosinophils 31-May-23 Adrenocortical Hormones 47

48. Control of Secretion • Hypothalamus – under the influence of higher centers – Releases Corticotrophin releasing hormone (CRH) 31-May-23 Adrenocortical Hormones 48 Limbic system CRH Hypotha lamus ACTH Adeno- hypophysis Plasma cortisol conc Adrenal cortex Negative feed back

49. Control of Secretion • CRH acts on anterior pituitary – Releases ACTH • ACTH acts on adrenal cortex (zona fasciculata) – Releases cortisol – Released into plasma 31-May-23 Adrenocortical Hormones 49 Limbic system CRH Hypotha lamus ACTH Adeno- hypophysis Plasma cortisol conc Adrenal corte Negative feed back

50. Control of Secretion • Conc of plasma cortisol – Negative feedback inhibition • Hypothalamus • Anterior pituitary 31-May-23 Adrenocortical Hormones 50 Limbic system CRH Hypotha lamus ACTH Adeno- hypophysis Plasma cortisol conc Adrenal corte Negative feed back

51. Response to Stress • Hypophysial adrenocortical response • Stress – Trauma, infection, haemorrhage, exercise acute anxiety • Produce higher level of cortisol 31-May-23 Adrenocortical Hormones 51 CRH ACTH Hypothalamus Adrenal cortex Cortisol  Anterior pituitary Stress

52. Questions?

53. Mineralocorticoids 31-May-23 Adrenocortical Hormones 53

54. Aldosterone • Secreted by the cells – of the zona glomerulosa • Functions –Increase Na+ re-absorption by • the kidneys, sweat glands, salivary glands, GIT –Increase excretion of K+, H+ 31-May-23 Adrenocortical Hormones 54

55. Mechanism of Action • Site of action –Act on the Principal cells –of the late distal tubules&Cortic al collecting duct 31-May-23 Adrenocortical Hormones 55 Na+ Na+ K+ Lumen ISF Na+

56. Mechanism of Action • Thus Aldosterone – Increase the number of Na-K ATPase molecules in the basal lateral membrane • Aldosterone increase the exchange of sodium and potassium – Na+ conservation in ECF – K+ is excreted 31-May-23 Adrenocortical Hormones 56 Na+ Na+ K+ Lumen ISF Na+

57. Control of Aldosterone Secretion • ECF volume/Blood volume • Arterial BP •  K+ conc in ECF leads to an  in aldosterone secretion •  Na+ conc in ECF inhibits aldosterone secretion 31-May-23 Adrenocortical Hormones 57

58. Atrial Natriuretic Peptide (ANP) • ANP inhibit production of –Renin –Aldosterone • Leads to a reduction of Na+ by the nephrons and hence –Increased Na+ excretion in urine 31-May-23 Adrenocortical Hormones 58

6.Adrenal galnds.ppt

6.Adrenal galnds.ppt

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6.Adrenal galnds.ppt