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Transcript
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” 1889- Charles Brown-Sequard Extract of Testes dissolved in H2O Steroid Hormones Lipid Soluble Placebo effect Intuitive observations Hormone replacement therapy 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 Young, T-Cells Location of Endocrine Glands Other hormone secreting cells located in: Leptin • Kidneys • Stomach e.g. Gastrin • Liver • Small Intestine • Heart e.g. ANP Decreased Appetite signal • Skin • Adipose Tissue • Placenta e.g. Progesterone Leptin Hormone synthesis: Post-translational modification Enzyme Fig 7.3-Silverthorn Catecholamine, Peptide and thyroid hormones Used as measure of insulin production C-peptide 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 Importance of receptors: For hormone to be active ‘Target cell’ must express specific receptor Upregulation Down-regulation Hyperinsulinemia - diabetes Hormone excess Homeostasis Receptor Blocking Hormone deficient E.g. RU486 (mifepristone) – Induces Abortion Blocks progesterone receptors Prevents uterine conditions embryo nurturing Types of Hormones 1: Water Soluble hormones Amines Peptides & Proteins Norepinephrine Posterior Pituitary Vasopressin Adrenal medulla Urine Output Increased Glucose uptake Insulin Pineal Gland Eicosanoids Pancreas Blood Glucose All Cell Types Except RBC Local Hormones Various effects e.g. vasodilatation 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 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 Mechanisms of Hormone Action 1. Steroid and thyroid hormone receptors Fig 7.7 From Silverthorn Mechanisms of Hormone action 2; Water soluble hormones NE, ACTH, FSH, LH etc. Activates Protein Kinases Fig 9.1. E.N. Marieb. The Major Endocrine Organs in adults 1 The Pituitary Gland 1. Posterior Fig 20-8 McCance The Major Endocrine Organs 1 The Pituitary Gland 2- Pituitary-hypothalamo relationship . CRH, GnRH Anterior Posterior The Major endocrine glands 2. The Pineal gland Pinealocytes Decreased Light Melatonin Melanopsin Circulation Brainstem Body target cells Metabolic rate Antioxidant? Promotes Sleep 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 The Major endocrine glands 4. : The Parathyroid gland 1. The Major endocrine glands 4. : The Parathyroid gland 2. PTH The Major endocrine glands 5. : The Pancreas 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 The Major endocrine glands 6. : The Adrenal gland 1 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 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 Testis ● Male 20 Sex Characteristics Inhibin – Inhibits FSH from Anterior Pituitary (negative feedback) 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.