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Lecture # 15: The Endocrine System 2

The Endocrine System (Chapter 17). Lecture # 15: The Endocrine System 2 . Objectives. 1- To identify the chemical classes to which various hormones belong. 2- To describe how hormones stimulates their target cells. Hormone Chemistry. Most hormones fall into three chemical classes: .

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Lecture # 15: The Endocrine System 2

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  1. The Endocrine System (Chapter 17) Lecture # 15: The Endocrine System 2 Objectives 1- To identify the chemical classes to which various hormones belong. 2- To describe how hormones stimulates their target cells.

  2. Hormone Chemistry Most hormones fall into three chemical classes: • 1- Steroids: They are derived from cholesterol. • 2- Peptides and Glycoproteins: They are chains of 3 to 200 or more aminoacids. • 3- Monoamines (biogenic amines): They are made from aminoacids and retain an amino group. • 1- Steroids: • They are secreted by gonads and adrenal glands. • Estrogens, progesterone, testosterone, cortisol, corticosterone, aldosterone, DHEA, and calcitriol are steroid hormones.

  3. Steroid hormones are derived from cholesterol.

  4. 2- Peptides and Glycoproteins • They are created from chains of amino acids. They are secreted by pituitary and hypothalamus. • Oxytocin, antidiuretic hormone, releasing and inhibiting hormones, and anterior pituitary hormones.

  5. 3- Monoamines (biogenic amines) • They are derived from amino acids and secreted by adrenal, pineal, and thyroid glands. • Epinephrine, norepinephrine, melatonin, and thyroid hormone are mono-amines. Aminoacid

  6. Hormone Receptors and Mode of Action Hormones stimulate only those cells that have receptors for them. Receptors are protein or glycoprotein molecules on plasma membrane, in the cytoplasm, or in the nucleus. Usually each target cell has a few thousand receptors for a given hormone. Receptors act like switches turning on metabolic pathways when hormone binds to them. Metabolic effects can be achieved by different mechanisms: 1- Activation of genes in the nucleus to initiate the transcription and synthesis of some proteins. 2- Activation of specific enzymes that are inactive in the cytosol. 3- Changes in the membrane permeability and membrane potentials.

  7. 1- Activation of genes in the nucleus to initiate the transcription and synthesis of some proteins. 2- Activation of specific enzymes that are inactive in the cytosol. Protein kinases are proteins present in the cytosol as inactive proteins. When protein kinases are activated they have the ability to activate many other enzymes.

  8. 3- Changes in the membrane permeability and membrane potentials.

  9. Hormone Receptors and Mode of Action Free hormones (hydrophilic) Receptor in plasma membrane Transport protein Second- messenger activation Bound hormones (hydrophobic) Target cell Tissue fluid Receptor in nucleus Hydrophilic Hormones (Peptides and Catecholamines) Hydrophobic Hormones (Steroids and Thyroid hormones) • 1- They cannot penetrate into target cell. • 1- They penetrate plasma membrane and enter nucleus. Blood • 2- They act directly on the genes changing target cell physiology. • 2- They must stimulate target cell physiology indirectly. • 3- It takes several hours to days to show effect due to lag for protein synthesis.

  10. Action of Hydrophobic Hormones The Action of Thyroid Hormone on a Target Cell 1- Thyroid hormone enters target cell by diffusion – mostly as T4with little metabolic effect. ThyroxineBinding Globulin 2- Within target cell, T4 is converted to more potent T3. 3- T3 enters target cells and binds to receptors in chromatin and acti-vates genes. • 4- Activated genes make a muscle protein (myosin) enhancing cardiac muscle response to sympathetic stimulation and strengthening heartbeat. • 5- Activated genes also make the enzyme Na+ - K+ATPase. One of its effects is to generate heat, thus accounting for the calorigenic effect of thyroid hormone.

  11. Action of Hydrophilic Hormones The hormone binds to a cell-surface receptor, which is linked to a second messenger system on other side of the membrane. Second messengers: 1- cAMP produced by the enzyme adenylatecyclase. 2- Diacylglycerol (DAG) and Inositol triphosphate (IP3) produced by the enzyme phospholipase. The enzymes adenylate cyclase and phospholipase are integral proteins of the plasma membrane of target cells.

  12. Cyclic AMP as a Second Messenger G proteins and Hormone Activity They are the first messengers that bind to receptors and leading to the appearance of a second messenger. Hormone Hormone Hormone They are glycoproteins of the plasma membrane that bind specific hormones and determine the cell’s hormonal sensitivity. Receptor Receptor G protein (activated) G protein G protein (inactive) It is an enzyme complex coupled to the plasma membrane, which is activated by the receptor-enzyme complex. Once it is activated, it activates the adenyl cyclase. Adenyl cyclase Adenyl cyclase Adenylate cyclase Receptor (activated) (inactive) ATP cAMP cAMP Protein kinase It is an enzyme that converts the ATP in cyclic AMP (cAMP) Protein kinase Protein kinase (activated) (Inactive) It is the second messenger that activates the enzymes protein kinases. Opens ion channels Activates enzymes They are enzymes that perform phosphorylations that activates or inactivates other enzymes

  13. Cyclic AMP as a Second Messenger Hormone–receptor binding activates a G protein. 1 2 3 4 5 6 G protein activates adenylatecyclase. Adenylate cyclase produces cAMP. cAMP activates proteinkinases. Protein kinases phosphorylate enzymes. This activates some enzymes and deactivates others. Activated enzymes catalyze metabolic reactions with a wide range of possible effects on the cell. • Metabolic reactions: • Synthesis • Secretion • Change membrane potentials

  14. Diacylglycerol (DAG) and Inositol Triphosphate (IP3) as Second Messengers A hormone binds to its receptor, which activates a G protein. 1 2 3 4 The G protein migrates to a phospholipase molecule and activates it. The phospholipase transforms a phospholipid molecule into DAG. DAG activates a protein kinase, an enzymes that phosphorylates other enzymes with various metabolic effects.

  15. A hormone binds to its receptor, which activates a G protein. 10 1 2 3 8 9 6 7 The G protein migrates to a phospholipase molecule and activates it. The IP3 raises calcium concentration in the cytosol in 2 ways: 1- IP3 opens gated channels in the plasma membrane. 2- IP3 opens gated channels in the endo-plasmic reticulum. The phospholipase transforms a phospholipid molecule into IP3. Ca2+ Calcium is a Third Messenger that can have three effects: Calcium may bind to other gated membrane channels and alter the membrane potential of the cells. Calcium may activate cytoplasmic enzymes that alter cell metabolism. Calcium may bind to the protein Cadmodulin, which activates a protein kinase.

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