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ENDOCRINE SYSTEM

ENDOCRINE SYSTEM. PHYSIOLOGY. Hormones. A chemical secreted by a cell or groups of cells into the blood for transport to a distant target where it exerts its effect at very low concentrations Types Peptide Hormones Growth Hormone, Insulin, Vasopressin Steroid Hormones

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ENDOCRINE SYSTEM

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  1. ENDOCRINE SYSTEM PHYSIOLOGY

  2. Hormones • A chemical secreted by a cell or groups of cells into the blood for transport to a distant target where it exerts its effect at very low concentrations • Types • Peptide Hormones • Growth Hormone, Insulin, Vasopressin • Steroid Hormones • Cortisol, Testosterone, Estrogen • Tyrosine Derivatives • Thyroxine and Epinephrine

  3. Endocrine vs. Nervous System • Major communication systems in the body • Integrate stimuli and responses to changes in external and internal environment • Both are crucial to coordinated functions of highly differentiated cells, tissues and organs • Unlike the nervous system, the endocrine system is anatomically discontinuous.

  4. Nervous system • The nervous systemexerts point-to-point control through nerves, similar to sending messages by conventional telephone. Nervous control is electrical in nature and fast.

  5. Hormones travel via the bloodstream to target cells • The endocrine systembroadcasts its hormonal messages to essentially all cells by secretion into blood and extracellular fluid. Like a radio broadcast, it requires a receiver to get the message - in the case of endocrine messages, cells must bear a receptor for the hormone being broadcast in order to respond.

  6. A cell is a target because is has a specific receptor for the hormone Most hormones circulate in blood, coming into contact with essentially all cells. However, a given hormone usually affects only a limited number of cells, which are called target cells. A target cell responds to a hormone because it bearsreceptorsfor the hormone.

  7. Mechanisms of Secretion Ca++ Neuron Ca++ Neurosecretory cell Capillary Ca++ Simple Endocrine Cell Ca++ Intracellular Ca stores

  8. Hormones • Types of Secretion • Autocrine – affects the secreting cell • Paracrine – affects neighbouring cell • Endocrine – secreted into bloodstream • Exocrine – secreted onto body surface, including surface of gut

  9. Response vs. Distance Traveled • Endocrine action:the hormone is distributed in blood and binds to distant target cells.Paracrine action:the hormone acts locally by diffusing from its source to target cells in the neighborhood.Autocrine action: the hormone acts on the same cell that produced it.

  10. Types of hormones • Hormones are categorized into four structural groups, with members of each group having many properties in common: • Steroids • Thyroid Hormones • Peptides and proteins • Amino acid derivatives= Catecholamines • Fatty acid derivatives - Eicosanoids

  11. Two types of hormones • Lipid Soluble • Steroid hormones (eg estrogen, testosterone) • Thyroid hormones • Lipid Insoluble • Peptides and Proteins (eg insulin) • Catecholamines (eg adrenalin)

  12. Two types of hormones • Lipid-soluble Carrier molecule Hormone molecule Cytoplasmic receptor Nuclear receptor Transcription & Translation long lasting effects Nucleus

  13. Two types of hormones • Lipid-insoluble Hormone molecule Plasma membrane receptor Second Messenger Effector Protein Cellular effects

  14. Peptide/protein hormones • Range from 3 amino acids to hundreds of amino acids in size. • Often produced as larger molecular weight precursors that are proteolytically cleaved to the active form of the hormone. • Peptide/protein hormones are water soluble. • Comprise the largest number of hormones– perhaps in thousands

  15. Peptide/protein hormones • Are encoded by a specific gene which is transcribed into mRNA and translated into a protein precursor called a preprohormone • Preprohormones are often post-translationally modified in the ER to contain carbohydrates (glycosylation) • Preprohormones contain signal peptides (hydrophobic amino acids) which targets them to the golgi where signal sequence is removed to form prohormone • Prohormone is processed into active hormone and packaged into secretory vessicles

  16. Amine hormones There are two groups of hormones derived from the amino acid tyrosine Thyroid hormones and Catecholamines

  17. Hypothalamus and pituitary gland

  18. Hypothalamus and pituitary gland

  19. Hypothalamus and posterior pituitary Midsagital view illustrates that magnocellular neurons paraventricular and supraoptic nuclei secrete oxytocin and vasopressin directly into capillaries in the posterior lobe

  20. Pituitary gland • Master gland • Secretes 9 hormones that control other glands • 2 distinct parts • Anterior pituitary (adenohypophysis) • Posterior pituitary (neurohypophysis) • Both parts controlled by neurosecretory cells of the hypothalamus (part of the brain!)

  21. Anterior pituitary:Adenohypophysis • Anterior pituitary: connected to the hypothalamus by the superior hypophyseal artery. • The antererior pituitary is an amalgam of hormone producing glandular cells. • The anterior pituitary produces six peptide hormones: prolactin, growth hormone (GH), thyroid stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH).

  22. Anterior Pituitary Hypothalamus Hormone 1 Portal blood vessels Hormone 1 Anterior Pituitary Target Tissue Hormone 2

  23. Posterior Pituitary Hypothalamus Hormone 1 Portal blood vessels Posterior Pituitary Target Tissue

  24. Neurosecretory neurons  Anterior Pituitary • Secrete hormones into portal blood vessels • Regulate secretion of other hormones from anterior pituitary • Neurosecretory neurons  Posterior Pituitary • Secrete hormones directly into capillaries

  25. Anterior Pituitary • 2 hormone system • 1st hormone stimulates or inhibits release of other hormones from anterior pituitary • 2nd hormone has effect on target tissue

  26. Examples: • 1st hormone • Corticotropin-releasing hormone (CRH) • Thyroid hormone releasing hormone (TRH) • Prolactin-inhibiting hormone (PIH) • 2nd hormone • Adrenocorticotropin hormone (ACTH) • Thyroid stimulating hormone (TSH) • Prolactin

  27. Posterior Pituitary • Neurosecretory cells secrete hormones directly onto capillaries • Only 2 hormones: • Antidiuretic hormone (ADH, also called vasopressin) • Water retention by the kidney • Oxytocin • Uterine contractions during childbirth • Milk ejection during breast feeding

  28. Hypothalamic releasing hormone Effect on pituitary Corticotropin releasing hormone (CRH) Stimulates ACTH secretion Thyrotropin releasing hormone (TRH) Stimulates TSH and Prolactin secretion Growth hormone releasing hormone (GHRH) Stimulates GH secretion Somatostatin Inhibits GH (and other hormone) secretion Gonadotropin releasing hormone (GnRH) a.k.a LHRH Stimulates LH and FSH secretion Prolactin releasing hormone (PRH) Stimulates PRL secretion Prolactin inhibiting hormone (dopamine) Inhibits PRL secretion Hypothalamic releasing hormones

  29. Thyroid

  30. Thyroid Hormone • Thyroid hormones are basically a "double" tyrosine with the critical incorporation of 3 or 4 iodine atoms. • Thyroid hormone is produced by the thyroid gland and is lipid soluble • Thyroid hormones are produced by modification of a tyrosine residue contained in thyroglobulin, post-translationally modified to bind iodine, then proteolytically cleaved and released as T4 and T3. T3 and T4 then bind to thyroxin binding globulin for transport in the blood

  31. Thyroid Hormones • Produced in the follicle cells of the thyroid • T3 triiodothyronine • T4 thyroxine • Both require iodine to be produced • Thyroid hormones increase metabolic rate in brain, muscle, heart, liver, kidney, etc. • Produces heat as a by-product

  32. Thyroid hormones

  33. Hypothyroid • Lack of iodine during fetal development • Stunted growth, called cretinism

  34. Hypothyroid • Lack of Iodine in diet • Lack of selenium in diet • Genetic defect on chromosome 15 • 15q25.3-26.1 • Receptor insensitivity • Increased Antibody levels • Due to Environmental Factors? • Decreased Adrenal Function

  35. Enlargement of the thyroid, called goiter Due to lack of thyroid hormones and overstimulation of the thyroid gland by TSH Because no negative feedback Thyroxine Triiodothyronine feedback on the Anterior Pituitary and Hypothalamus to decrease TSH levels If TSH levels are high then there is a lack of negative feedback A lack of negative feedback means low T4, T3 levels in the circulation.

  36. Hoshimoto’s Thyroiditis • Increased sensitivity to cold • Constipation • Pale, dry skin • A puffy face • Hoarse voice • An elevated blood cholesterol level • Unexplained weight gain — occurring infrequently and rarely more than 10 to 20 pounds, most of which is fluid • Muscle aches, tenderness and stiffness, especially in your shoulders and hips • Pain and stiffness in your joints and swelling in your knees or the small joints in your hands and feet • Muscle weakness, especially in your lower extremities • Excessive or prolonged menstrual bleeding (menorrhagia) • Depression

  37. Control of Thyroid If –’ve feedback lost Too much TSH Get goiter Cold Hypothalamic neurons Thyroid releasing hormone (TRH) Anterior Pituitary Thyroid Stimulating Hormone (TSH) Thyroid Release of thyroid hormones – T3 and T4

  38. Hyperthyroid • Also known as Graves’ Disease • Excessive secretion of T4 • An antibody called thyrotropin receptor antibody (TRAb) stimulates the thyroid to make excessive amounts of thyroid hormone.

  39. Graves’ Disease • Anxiety • Irritability • Difficulty sleeping • Fatigue • A rapid or irregular heartbeat • A fine tremor of your hands or fingers • An increase in perspiration • Sensitivity to heat • Weight loss, despite normal food intake • Brittle hair • Enlargement of your thyroid gland (goiter) • Light menstrual periods • Frequent bowel movements

  40. Control of extracellular Calcium • Two hormones • Parathyroid hormone • Calcitonin

  41. Parathyroid Gland

  42. Parathyroid • Low blood Ca++ stimulates release of parathyroid hormones • Act to increase blood Ca++ by •  Ca++ release from bone •  Ca++ absorption in gut •  Ca++ reabsorption in kidney

  43. Calcitonin • Produced in parafollicular cells of the thyroid gland • High Blood Ca++ stimulates release of calcitonin • Act to decrease blood Ca++ by • ↓ Ca++ release from bone • ↓ Ca++ reabsorption in kidney

  44. High Ca++ Low Ca++ Calcitonin Parathyroid hormone Reabsorb Ca In the kidney Mobilize Ca From Bone Increase absorption of Ca from intestine

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