Introduction to Endocrinology Bill Montague Medical & Social Care Education MSB G18 [email_address] uk http://www.le.ac.uk...
Plan of Sessions <ul><li>Introduction to Endocrinology </li></ul><ul><li>Thyroid </li></ul><ul><li>Adrenal and Anterior Pi...
Cell communication <ul><li>Human body composed of functionally specialised cells & tissues.  </li></ul><ul><li>Normal func...
Components of the endocrine system <ul><li>Endocrine tissue </li></ul><ul><li>Biologically active chemical </li></ul><ul><...
Endocrine glands
Major classes of hormones in man <ul><li>4  classes identified on structural grounds: </li></ul><ul><li>polypeptide hormon...
Importance of structure <ul><li>Structure determines: </li></ul><ul><li>how they are made, stored & secreted. </li></ul><u...
Protein hormones - polypeptides <ul><li>Largest group. </li></ul><ul><li>Most consist of a single chain of amino acids. </...
Protein hormones - glycoproteins <ul><li>4 hormones: </li></ul><ul><li>thyroid stimulating hormone (TSH). </li></ul><ul><l...
Protein hormones (polypeptide & glycoprotein) <ul><li>Synthesised as larger precursor molecules (prohormone). </li></ul><u...
Amino acid derivatives <ul><li>Small molecules synthesised from  tyrosine . </li></ul>HO CH 2 CH(NH 2 )COOH
Amino acid derivatives <ul><li>Adrenaline (catecholamine) </li></ul><ul><li>Stored in vesicles in adrenal medulla. </li></...
Amino acid derivatives <ul><li>Thyroid hormones </li></ul><ul><li>Tri-iodothyronine (T3) </li></ul><ul><li>Tetra-iodothyro...
Thyroid hormones <ul><li>Stored extracellularly in thyroid follicles. </li></ul><ul><li>Hydrophobic : </li></ul><ul><li>re...
Steroid hormones <ul><li>All synthesised from cholesterol (C 27 ).  </li></ul><ul><li>Cholesterol stored in steroid produc...
Steroid hormones <ul><li>Steroid hormones vary: </li></ul><ul><li>number of C-atoms (27, 21,19 or 18). </li></ul><ul><li>n...
 
Classes of steroid hormones <ul><li>C-27 </li></ul><ul><li>Calciferols -  1,25-dihydroxycholecalciferol  (vitamin D) </li>...
Steroid hormones <ul><li>Not stored: </li></ul><ul><li>synthesised on demand from cholesterol esters stored as lipid dropl...
Steroid hormone synthesis Cholesterol ester Cholesterol Progesterone 7-dehydrocholesterol Testosterone Aldosterone Cortiso...
Components of the endocrine system <ul><li>Endocrine tissue </li></ul><ul><li>Biologically active chemical </li></ul><ul><...
Hormone concentrations in blood <ul><li>Hormone concentration normally low (10 -10  - 10 -8  M) but can increase dramatica...
Control of hormone secretion <ul><li>Rate of secretion usually controlled by negative feedback: </li></ul><ul><li>change i...
Control of hormone secretion by change in a parameter regulated by the hormone. <ul><li>  </li></ul><ul><li>  insulin </li...
Control of hormone secretion by change in a parameter regulated by the hormone. <ul><li>  </li></ul><ul><li>     insulin ...
Control of hormone secretion by change in a parameter regulated by the hormone. <ul><li>  </li></ul><ul><li>     insulin ...
Control of hormone secretion by concentration of hormone itself or another hormone <ul><li>  Cortisol </li></ul><ul><li>  ...
Control of hormone secretion by concentration of hormone itself or another hormone <ul><li>     Cortisol </li></ul><ul><l...
Control of hormone secretion by concentration of hormone itself or another hormone <ul><li>     Cortisol </li></ul><ul><l...
Control of hormone secretion by concentration of hormone itself or another hormone <ul><li>     Cortisol </li></ul><ul><l...
Hormone transport <ul><li>Hydrophobic hormones need transport proteins. </li></ul><ul><li>Dynamic equilibrium between boun...
Hormone action <ul><li>Hormones act by binding to receptors on/in target cells. </li></ul><ul><li>Magnitude of response de...
Mechanism of hormone action Response P  R  S 2 nd  messenger nucleus S S DNA R R mRNA Plasma membrane P
Target tissue responses <ul><li>Speed of response varies: </li></ul><ul><li>quick (sec-min) - activation of existing enzym...
Hormone inactivation <ul><li>Steroid hormones & amino acid derivatives: </li></ul><ul><li>Small change in structure - incr...
Hormone functions <ul><li>Control: </li></ul><ul><li>Growth, development & reproduction. </li></ul><ul><li>Homeostasis - n...
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Introduction to Endocrinology Bill Montague

  1. 1. Introduction to Endocrinology Bill Montague Medical & Social Care Education MSB G18 [email_address] uk http://www.le.ac.uk/bs/resources/
  2. 2. Plan of Sessions <ul><li>Introduction to Endocrinology </li></ul><ul><li>Thyroid </li></ul><ul><li>Adrenal and Anterior Pituitary </li></ul><ul><li>Tutorial – clinical case studies. </li></ul><ul><li>Endocrine pancreas and the control of energy metabolism. </li></ul>
  3. 3. Cell communication <ul><li>Human body composed of functionally specialised cells & tissues. </li></ul><ul><li>Normal function depends on these components working together. </li></ul><ul><li>Coordination achieved by communication systems: </li></ul><ul><li>endocrine </li></ul><ul><li>nervous </li></ul><ul><li>immune </li></ul><ul><li>All communication systems: </li></ul><ul><li>use chemical signals (nervous system also uses electrical signals). </li></ul><ul><li>work together, not in isolation. </li></ul>
  4. 4. Components of the endocrine system <ul><li>Endocrine tissue </li></ul><ul><li>Biologically active chemical </li></ul><ul><li>Transport in blood </li></ul><ul><li>Target cells (receptors & response) </li></ul><ul><li>Inactivation of chemical </li></ul>
  5. 5. Endocrine glands
  6. 6. Major classes of hormones in man <ul><li>4 classes identified on structural grounds: </li></ul><ul><li>polypeptide hormones (>20). </li></ul><ul><li> </li></ul><ul><li>glycoprotein hormones (4). </li></ul><ul><li>amino acid derivatives (3 major hormones). </li></ul><ul><li>steroid hormones (~10). </li></ul>proteins
  7. 7. Importance of structure <ul><li>Structure determines: </li></ul><ul><li>how they are made, stored & secreted. </li></ul><ul><li>how they are transported in the blood. </li></ul><ul><li>how they affect their target tissue(s). </li></ul><ul><li>how they are inactivated. </li></ul>
  8. 8. Protein hormones - polypeptides <ul><li>Largest group. </li></ul><ul><li>Most consist of a single chain of amino acids. </li></ul><ul><li>Vary in size (number of amino acids): </li></ul><ul><li>large = 191 - growth hormone. </li></ul><ul><li>medium = 51 - insulin (two chains – covalently linked). </li></ul><ul><li>small = 3 - thyrotropin releasing hormone. </li></ul>
  9. 9. Protein hormones - glycoproteins <ul><li>4 hormones: </li></ul><ul><li>thyroid stimulating hormone (TSH). </li></ul><ul><li>follicle stimulating hormone (FSH). </li></ul><ul><li>luteinizing hormone (LH). </li></ul><ul><li>human chorionic gonadotropin (hCG). </li></ul><ul><li>Consist of 2 polypeptide chains (  &  -subunits) with carbohydrate side chains. </li></ul>
  10. 10. Protein hormones (polypeptide & glycoprotein) <ul><li>Synthesised as larger precursor molecules (prohormone). </li></ul><ul><li>converted to smaller biologically active hormone during storage. </li></ul><ul><li>Stored in vesicles prior to secretion. </li></ul><ul><li>Hydrophilic : </li></ul><ul><li>easily transported in blood. </li></ul><ul><li>do not readily cross cell membranes - receptors on surface of target cells. </li></ul><ul><li>require intracellular signals (2 nd messengers). </li></ul>
  11. 11. Amino acid derivatives <ul><li>Small molecules synthesised from tyrosine . </li></ul>HO CH 2 CH(NH 2 )COOH
  12. 12. Amino acid derivatives <ul><li>Adrenaline (catecholamine) </li></ul><ul><li>Stored in vesicles in adrenal medulla. </li></ul><ul><li>Hydrophilic (weak) : </li></ul><ul><li>easily transported. </li></ul><ul><li>requires cell surface receptors & intracellular messengers. </li></ul><ul><li> </li></ul><ul><li> HO </li></ul><ul><li> HO CH(OH)-CH 2 -NH(CH 3 ) </li></ul>
  13. 13. Amino acid derivatives <ul><li>Thyroid hormones </li></ul><ul><li>Tri-iodothyronine (T3) </li></ul><ul><li>Tetra-iodothyronine (T4) = thyroxine </li></ul><ul><li> </li></ul><ul><li> </li></ul><ul><li> HO O CH 2 -CH(NH 2 )-COOH </li></ul><ul><li> </li></ul><ul><li> </li></ul>I I I I
  14. 14. Thyroid hormones <ul><li>Stored extracellularly in thyroid follicles. </li></ul><ul><li>Hydrophobic : </li></ul><ul><li>require transport proteins. </li></ul><ul><li>cross cell membranes - intracellular receptors. </li></ul>
  15. 15. Steroid hormones <ul><li>All synthesised from cholesterol (C 27 ). </li></ul><ul><li>Cholesterol stored in steroid producing tissues as cholesterol esters (cholesterol + fatty acid). </li></ul>
  16. 16. Steroid hormones <ul><li>Steroid hormones vary: </li></ul><ul><li>number of C-atoms (27, 21,19 or 18). </li></ul><ul><li>number of double bonds. </li></ul><ul><li>presence and type of side-groups. </li></ul>
  17. 18. Classes of steroid hormones <ul><li>C-27 </li></ul><ul><li>Calciferols - 1,25-dihydroxycholecalciferol (vitamin D) </li></ul><ul><li>C-21 </li></ul><ul><li>Corticosteroids – adrenal cortex </li></ul><ul><ul><li>Gluco-corticoids ( cortisol ) </li></ul></ul><ul><ul><li>Mineralo-corticoids ( aldosterone ) </li></ul></ul><ul><li>Progestins - progesterone (all steroid producing tissues) </li></ul><ul><li>C-19 </li></ul><ul><li>Androgens - testes, ovary, adrenal cortex ( testosterone ) </li></ul><ul><li>C-18 </li></ul><ul><li>Oestrogens – ovary ( oestradiol ) </li></ul>
  18. 19. Steroid hormones <ul><li>Not stored: </li></ul><ul><li>synthesised on demand from cholesterol esters stored as lipid droplets. </li></ul><ul><li>synthesis involves activation of enzymes in synthetic pathway. </li></ul><ul><li>Hydrophobic molecules </li></ul><ul><li>require transport proteins. </li></ul><ul><li>able to cross cell membranes – receptors are intracellular (cytoplasmic and/or nuclear). </li></ul><ul><li>Control rate of transcription of specific genes. </li></ul>
  19. 20. Steroid hormone synthesis Cholesterol ester Cholesterol Progesterone 7-dehydrocholesterol Testosterone Aldosterone Cortisol Calciferols Oestradiol
  20. 21. Components of the endocrine system <ul><li>Endocrine tissue </li></ul><ul><li>Biologically active chemical </li></ul><ul><li>Transport in blood </li></ul><ul><li>Target cells (receptors & response) </li></ul><ul><li>Inactivation of chemical </li></ul>
  21. 22. Hormone concentrations in blood <ul><li>Hormone concentration normally low (10 -10 - 10 -8 M) but can increase dramatically depending on: </li></ul><ul><li>rate of secretion. </li></ul><ul><li>extent of binding to carrier proteins. </li></ul><ul><li>rate of inactivation & excretion. </li></ul>
  22. 23. Control of hormone secretion <ul><li>Rate of secretion usually controlled by negative feedback: </li></ul><ul><li>change in a parameter regulated by the hormone. </li></ul><ul><li>concentration of hormone itself or another hormone. </li></ul><ul><li> </li></ul>
  23. 24. Control of hormone secretion by change in a parameter regulated by the hormone. <ul><li> </li></ul><ul><li> insulin </li></ul><ul><li> </li></ul><ul><li> </li></ul> -cell muscle [blood glucose]
  24. 25. Control of hormone secretion by change in a parameter regulated by the hormone. <ul><li> </li></ul><ul><li>  insulin </li></ul><ul><li> </li></ul><ul><li>  </li></ul> -cell muscle  [blood glucose]
  25. 26. Control of hormone secretion by change in a parameter regulated by the hormone. <ul><li> </li></ul><ul><li>  insulin </li></ul><ul><li> </li></ul><ul><li> </li></ul> -cell muscle  [blood glucose]
  26. 27. Control of hormone secretion by concentration of hormone itself or another hormone <ul><li> Cortisol </li></ul><ul><li> </li></ul><ul><li> </li></ul><ul><li> ACTH </li></ul>Adrenal Anterior Pituitary
  27. 28. Control of hormone secretion by concentration of hormone itself or another hormone <ul><li>  Cortisol </li></ul><ul><li> + </li></ul><ul><li> ACTH </li></ul>Adrenal Anterior Pituitary
  28. 29. Control of hormone secretion by concentration of hormone itself or another hormone <ul><li>  Cortisol </li></ul><ul><li> </li></ul><ul><li> ACTH </li></ul>Adrenal Anterior Pituitary
  29. 30. Control of hormone secretion by concentration of hormone itself or another hormone <ul><li>  Cortisol </li></ul><ul><li>  </li></ul><ul><li> ACTH </li></ul>Adrenal Anterior Pituitary
  30. 31. Hormone transport <ul><li>Hydrophobic hormones need transport proteins. </li></ul><ul><li>Dynamic equilibrium between bound and free forms of hormone: </li></ul><ul><li>H (free) + BP  H-BP (bound) </li></ul><ul><li>Only free form biologically active. </li></ul>
  31. 32. Hormone action <ul><li>Hormones act by binding to receptors on/in target cells. </li></ul><ul><li>Magnitude of response depends on: </li></ul><ul><li>concentration of active hormone at target tissue. </li></ul><ul><li>receptor number (can be varied). </li></ul><ul><li>affinity of receptor for hormone. </li></ul><ul><li>degree of signal amplification (enzymes involved). </li></ul>
  32. 33. Mechanism of hormone action Response P R S 2 nd messenger nucleus S S DNA R R mRNA Plasma membrane P
  33. 34. Target tissue responses <ul><li>Speed of response varies: </li></ul><ul><li>quick (sec-min) - activation of existing enzymes & other functional proteins. </li></ul><ul><li>slow (hr-days) - synthesis of new enzymes & functional proteins. </li></ul>
  34. 35. Hormone inactivation <ul><li>Steroid hormones & amino acid derivatives: </li></ul><ul><li>Small change in structure - increased water solubility. </li></ul><ul><li>Products excreted (bile, urine). </li></ul><ul><li>Protein hormones: </li></ul><ul><li>Large change in structure – degraded to amino acids. </li></ul><ul><li>Products reused or broken down. </li></ul><ul><li>Tissues involved: </li></ul><ul><li>Target tissues. </li></ul><ul><li>Liver (products in bile & blood). </li></ul><ul><li>Kidney (products in urine). </li></ul>
  35. 36. Hormone functions <ul><li>Control: </li></ul><ul><li>Growth, development & reproduction. </li></ul><ul><li>Homeostasis - nutrient & electrolyte. </li></ul><ul><li>Response to external stimuli (stress, trauma). </li></ul><ul><li>Complex control processes: </li></ul><ul><li>many processes controlled by several hormones. </li></ul><ul><li>many hormones have several effects. </li></ul><ul><li>Failure in these control systems can occur producing clinical problems: </li></ul><ul><li>Diabetes, Thyroid disease, Cushing’s & Addison’s diseases </li></ul><ul><li>Infertility </li></ul>
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