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Endocrine introduction

Introduction to the endocrine system

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Endocrine introduction

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  1. Endocrine Glands: Chemical Classification of Hormones (Insulin, Glucagon, PTH) • Most Hormones are peptides E.g. Thyroid Hormone (TH)

  2. Endocrine Glands: Chemical Classification of Hormones; Monoamines e.g. TH • Hydrophilic • Don’t need a transport protein while being transported in the blood • Find their target cell and bind to plasma membrane (PM) Receptor (R) to produce action (more later) • Exception is TH which is hydrophobic • Synthesized from the amino acids: • Tyrosine  monoamine hormone: TH, Epinephrine and Norepinephrine • Tryptophan  monoamine hormone: melatonin and serotonin

  3. Endocrine Glands: Chemical Classification of Hormones; Steroid Hormones • Cholesterol is essential for steroid H synthesis • Hydrophobic; require transport proteins in blood (plasma is 90% H2O) • When released from the transport protein they can cross the plasma membrane (PM) of the target cell  • Bind to an Intracellular receptor and activate DNA

  4. Endocrine Glands and Calcium Homeostasis : The Thyroid and Parathyroid Glands Homeostatic [Ca2+]blood ~ 9.2–10.4 mg/dL Pharynx (posterior) • Thyroid gland Follicular cells make and secrete TH • Thyroid gland Parafollicular C-cells make and secrete calcitonin hormone • Parathyroid • Gland (4) chief cells make and secrete • Parathyroid hormone (PTH) Esophagus Trachea (a) Both the Thyroid and Parathyroid Glands are Endocrine Glands

  5. The Stimulus: Hypocalcemia Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Blood Ca2+ returns to normal Blood Ca2+ deficiency Parathyroid hormone secretion Increased osteoclast activity Increases resorption Reduced osteoblast activity Decreases deposition More urinary phosphate excretion Prevention of hydroxyapatite formation Less urinary calcium excretion Conservation of calcium (b) Correction for hypocalcemia

  6. The Stimulus: Hypercalcemia Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Blood Ca2+ excess Blood Ca2+ returns to normal Calcitonin secretion Reduced osteoclast activity Less bone resorption Increased osteoblast activity More bone deposition (a) Correction for hypercalcemia

  7. Hormone Travel: Overview Free There are 2 categories of H’s in terms of their solubility and mode of transport: Hydrophilic H’s Hydrophobic H’s Free H’s are active; they can bind to R’s on cells or inside cells Transport protein-bound H’s are not active Free Activates DNA when bound to R

  8. Transport Proteins and Half-life (T1/2) Transport proteins: • Carry hydrophobic H’s: e.g. Steroids & TH • T1/2 : The time it takes for the level of a H in the blood to ↓ by 50% • Transport proteins  T1/2 :  time that H acts • Albumins & globulins are transport proteins made in liver

  9. Hydrophobic/Lipophilic H’s Hydrophobic/Lipophilic H’s (e.g. Steroid H’s, Aldosterone, TH) once unbound from their transport proteins can freely cross the PM. These H’s bind to R’s in the cytoplasm or nucleus • H/R complex acts as a transcription factor • Binds to response element in DNA • Initiates transcription (mRNA production) • Increases protein synthesis

  10. Hydrophilic/lipophobic Hormones • H Can NOT cross the PM • H Binds to a PM R • H/R activates second messenger system inside cell which: Affects cellular activities • E.g., 2nd messenger can activate kinases: enzyme that phosphorylates proteins • Enzymes are reusable tools

  11. Signal Initiation and Amplification: GPCR • CRH + synthesis of ACTH • ACTH + the synthesis of Cortisol • TSH + the synthesis of a majority of T4 • LH + follicular maturation and ovulation ; + testosterone production and spermatogenesis • FSH + follicular development; + spermatogenesis • Hydrophillic GPCR is relatively quick (vs. hydrophobic mechanism)

  12. Amplification and GPCR’s • Amplification is: • Turning on 1 single hormone molecule which results in the production of many product molecules.

  13. Modulation of target cell sensitivity by up and down-regulation is proportionate to [R] • Up-regulation:  target cell response by  R density • Cell can overcome saturation of R’s with  R density if it needs to continue to respond • Down-regulation:  target cell response by  R density

  14. Example of up-regulation • Estrogen (from ovary) stimulates  • Uterine cells to ↑ progesterone receptors (PR) • Progesterone (from ovary) binds to PR • Uterus can now respond to P • Cascade leads to glycogen production by uterus • ↑ glycogen is good if pregnant • Permissive effect = E permits P to have effect

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