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Endocrine Physiology 1 Chapter 11 Chapter Outline Hormones and precursors (prohormones and prehormones) Chemical classes: amines, peptides, glycoproteins and steroids Hormonal interactions: permissive, synergistic and antagonistic Hormone concentration: abnormal high concentrations and desensitized target cells Mechanisms of hormonal actions: Lipophilic and polar hormones Pituitary gland: tropic/trophic hormones and Hypothalamus: releasing / inhibiting hormones Adrenal Glands Thyroid and Parathyroid glands Pancreas and other endocrine glands: pineal, gastrointestinal tract, gonads, and placenta Autocrine and Paracrine regulation: somatomedins, Nitric oxide, neutrophins, interleukins, and prostglandins Hormones, Prohormones and Prehormones Hormones: The endocrine system uses chemical messengers called hormones always secreted by ductless glands = endocrine into surrounding extracellular fluids and reach blood from there. Blood carries hormones to non-adjacent cells called target cells. Target cells have specific receptors for particular hormones and undergo changes when hormone binds to the receptor. Prohormones are formed inside ER by cleaving bigger proteins formed by ribosomes active hormones inside golgi apparatus Prehormones are released by endocrine gland and modified by another organ to active hormone Chemical classes of hormones Polar or Hydrophilic hormones transport dissolved in water in plasma of blood. Amines: epinephrine, norepinephrine Peptides/polypeptides: ADH and Oxytocin = 8 amino acids; insulin = 21 and 30 amino acids in 2 chains, glucagon = 29 amino acids, ACTH = 39 amino acids, PTH = 84 amino acids Glycoproteins = FSH, LH, TSH Lipophilic Hormones: cannot dissolve in water and attach to transport proteins in plasma. Thyroid hormones: Steroid hormones: Lipophilic Hormones Lipid soluble Receptors inside cytosol or nucleus Act by modifying gene- expression Examples include steroid and thyroid hormones Signal Transduction Pathway - lipid-soluble messenger Messenger passes the cell membrane and binds to the receptor mostly in nucleus, sometimes in cytosol. Activated receptor acts as a Transcription Factor. Activated-receptor binds to a specific sequence = Response Element near a gene. This binding alters the rate of transcription of that gene. It means if already active it can slow down or stop the transcription. On the contrary, if not going on, it can turn on the transcription or speed it up. If transcription is turned on m-RNA goes out in the cytosol and produces a new protein which can act as an enzyme or receptor or a channel or a secretory protein and so on. This shows up as cellular changes. Hydrophilic Hormones Peptide/protein and catecholamine hormones 4 kinds of Receptors for water soluble messengers. Water soluble messengers are polar substances and cannot enter the cell membrane. Therefore their receptors are present on the cell membrane. 4 kinds of receptors are: A ligand gated Channel – Na+ channel in postsynaptic membrane Receptor is an enzyme – Tyrosine kinase – insulin hormone and glucose absorption (Activate cytosolic JAK kinase) Interact with plasma membrane bound G-protein. G-protein complex has α, β, and γ units. Hormone attaches to G-protein and releases α of 3 units and activate membrane bound enzyme (adenylate cyclase) to change into ATP cAMP (2nd messenger). The phospholipase C-Ca2+ second messenger system: Role of Epinephrine Epinephrine has α and β adrenergic receptors. Epinephrine uses two 2nd messengers cAMP and calmodulin. Binding to β-adrenergic receptor activates enzyme adenylase cyclase. It converts ATP to cAMP. cAMP activates Protein Kinase. Binding of epinphrine to α-adrenergic receptor opens Ca2+ channel which attaches to Calmodulin and activates Protein kinase. Active Protein Kinase initiates breakdown of Glycogen to cause release of glucose from liver cell. Action of Insulin: Tyrosine Kinase is a membrane bound enzyme for Insulin. Insulin attaches to tyrosine kinase leading to its phosphorylation. Activated enzyme now uses ATP to phosphorylation of signal molecules. Cascade of effects causes up-regulation of transport proteins for glucose. It leads to uptake of glucose and anabolism. Fig 6.17 Role of Vitamin D3: 1, 25-dihydroxyvitamin D3 is active form of Vitamin D3. Skin produces a prehormone Vitamin D3 by using UV rays of sunlight. An enzyme in liver adds a hydroxyl group at carbon 25. Another enzyme in kidney, adds 2nd hydroxyl group at carbon 1 to produce active hormone 1, 25-dihydroxyvitamin D3. 7-dyhdrocholesterol vitamin D3 25-hydroxy vitamin D3 1, 25-dihydroxyvitamin D3 Effects of 1, 25-dihydroxyvitamin D3 increases absorption of Ca2+ and PO4-3 by intestine. Promotes formation of hydroxyapatite crystals in bone Promotes formation of osteoclasts and bone resorption when Ca2+ is low.