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CH0576: The Biology of Disease-Dr Richard N. Ranson

Endocrine Disorders 1. Goiter. CH0576: The Biology of Disease-Dr Richard N. Ranson. Historical Perspectives 1: the first endocrine experiment. A. A. Berthold 1849 – Concluded that testes secreted something that conditioned blood. Historical Perspectives 2: “Sexual Rejuvenation”.

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CH0576: The Biology of Disease-Dr Richard N. Ranson

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  1. Endocrine Disorders 1. Goiter CH0576: The Biology of Disease-Dr Richard N. Ranson

  2. Historical Perspectives 1: the first endocrine experiment A. A. Berthold 1849 – Concluded that testes secreted something that conditioned blood

  3. Historical Perspectives 2: “Sexual Rejuvenation” 1889- Charles Brown-Sequard Extract of Testes dissolved in H2O Steroid Hormones Lipid Soluble Placebo effect Intuitive observations Hormone replacement therapy

  4. Basic definitions: Endocrinology: • Hormones • Receptors • Signalling pathways • Diseases/pathophysiology Hormone: (hormon = to excite or get moving): • Molecule secreted from endocrine cells that regulates activity of target cells

  5. Young, T-Cells Location of Endocrine Glands

  6. Other hormone secreting cells located in: Leptin • Kidneys • Stomach e.g. Gastrin • Liver Decreased Appetite signal • Small Intestine • Heart e.g. ANP • Skin Leptin • Adipose Tissue • Placenta e.g. Progesterone

  7. Hormone synthesis: Post-translational modification Enzyme Fig 7.3-Silverthorn Catecholamine, Peptide and thyroid hormones Used as measure of insulin production C-peptide

  8. Hormone release - Local or circulating. Fig 18.2 Tortora & Derrickson Effects: Mins to hrs Rapid inactivation ● Example Local Hormone NO (Nitric Oxide) – Blood Vessel endothelial cells ● Acts on Smooth muscle – Vasodilatation ● Viagra enhances NO effects – Role in penile erection

  9. Importance of receptors: For hormone to be active ‘Target cell’ must express specific receptor Up-regulation Down-regulation Hyperinsulinemia - diabetes Hormone excess Homeostasis Hormone deficient E.g. RU486 (mifepristone) – Induces Abortion Blocks progesterone receptors Prevents uterine conditions embryo nurturing Receptor Blocking

  10. Types of Hormones 1: Water Soluble hormones Amines Peptides & Proteins Eicosanoids Posterior Pituitary Norepinephrine Urine Output Vasopressin All Cell Types Except RBC Adrenal medulla Increased Glucose uptake Local Hormones Various effects e.g. vasodilatation Insulin Blood Glucose Pineal Gland Pancreas

  11. Types of Hormones 2: Lipid Soluble Hormones Testosterone Steroid Hormones Testes, Adrenal Cortex Progesterone, Oestrogen (Ovaries) Thyroid Hormones Thyroid Gland Nitric Oxide - Endothelial Cells HRT-Oral administration-cross intestinal lining

  12. Transport of Hormones in Blood Water soluble circulate in blood plasma in ‘free’ form Lipid Soluble bound to transport proteins (synthesized in liver) ● Makes lipid hormones ‘water soluble’ ● Increases half life of hormone by protecting from enzyme degradation ● 0.1-10% hormone is unbound – “Free fraction” – leaves blood to react with cells

  13. Mechanisms of Hormone Action 1. Steroid and thyroid hormone receptors Fig 7.7 From Silverthorn

  14. Mechanisms of Hormone action 2; Water soluble hormones NE, ACTH, FSH, LH etc. Activates Protein Kinases Fig 9.1. E.N. Marieb.

  15. The Major Endocrine Organs in adults 1 The Pituitary Gland 1. Posterior Fig 20-8 McCance

  16. The Major Endocrine Organs 1 The Pituitary Gland 2- Pituitary-hypothalamo relationship . CRH, GnRH Anterior Posterior

  17. The Major endocrine glands 2. The Pineal gland Pinealocytes Decreased Light Melatonin Melanopsin Circulation Body target cells Brainstem Metabolic rate Antioxidant? Promotes Sleep

  18. The Major endocrine glands 3. : The thyroid gland T3, triiodothyronine T4, thyroxine Colloid TYr Iodine Stimulate metabolic rate Increase protein synthesis etc. Lack of Iodine in Diet (seafood) results in goiter

  19. The Major endocrine glands 4. : The Parathyroid gland 1.

  20. The Major endocrine glands 4. : The Parathyroid gland 2. PTH

  21. The Major endocrine glands 5. : The Pancreas

  22. The Major endocrine glands 5. : The Pancreas cont… Raises Blood Glucose Lowers Blood Glucose Paracrine-inhibits glucagon & Insulin Inhibits SOM, gallbladder contraction Pathophysiology- Diabetes Mellitus

  23. The Major endocrine glands 6. : The Adrenal gland 1

  24. The Major endocrine glands 6. : The Adrenal gland 2 Stress & Exercise Metabolism ● Increased HR ● Increased CO ● Blood to Muscles ● Dilate Airways Adr, NA Promotes Gluconeogenesis Anti-inflammatory Immunosuppressive (transplants) Cortisol

  25. The Major endocrine glands 7. : The Gonads Estrogens & Progesterone ● Menstrual Cycle ● Maintain pregnancy & Prep Mammary glands ● Female 20 Sex Characteristics Ovary Relaxin Dilates uterine cervix Testosterone ● Stimulates testis descent ● Regulates spermatogenesis ● Male 20 Sex Characteristics Testis Inhibin – Inhibits FSH from Anterior Pituitary (negative feedback)

  26. References Hadley, M.C. & Levine J.E. (2007). Endocrinology. 6th Edit, Pearson International. McCance, K. L. & Huether, S. E. (2006). Pathophysiology. (The Biologic Basis for Disease in Adults and Children). 5th Edit. Elsevier Mosby. Marieb, E. N. (2009) Essentials of Human Anatomy & Physiology. 9th Edit, Pearson International Purves, D et al (2008). Neuroscience. 4th Edit. Sinauer. Tortora G. J. & Derrickson B.(2006). Principles of Anatomy and Physiology. 11th Edit, Wiley. Unglaub Silverthorn D. (2007) Human Physiology (An integrated approach), 4th Edit, Pearson International.

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