Lecture # 1

1. Lecture # 1 The Endocrine System - 1 Chapter 18 Objectives: 1- To define hormone and endocrine system. 2- To describe the structural classification of the hormones. 3- To describe the two general mechanisms of hormone action.

2. Homeostasis It is the ability of the human body to maintain relatively stable internal conditions (temperature, pH, fluid balance, etc) even though the outside world changes continuously. Temperature: - 200 C Example: The body temperature must be near to 370C (98.60 F). When temperature increases only three degrees (to 400C), the organism is in danger. Temperature: + 500 C

6. Differences Between the Nervous and the Endocrine Systems Similarities Between the Nervous and the Endocrine System Communications Several chemicals function as both hormones and neurotrans-mitters: • Nervous: Both electrical and chemical • Endocrine: Only chemical • Norepinephrine, epinephrine, and dopamine. Speed and persistence of response Both systems are regulate by negative feedback control mechanisms. • Nervous: It reacts quickly (1 - 10 msec), stops quickly Both systems continually regulate each other: • Endocrine: It reacts slowly (hormone release in seconds or days), effect may continue for weeks • Neurons trigger hormone secretion and hormones stimulate or inhibit neurons Area of effect Target organs or cells: • Nervous: The effect is targeted and specific (one organ) Only those organs or cells that have receptors for a neurotransmitter or a hormone can respond to it. • Endocrine: The effect is more general, widespread effects (many organs)

7. The Endocrine System Regulates Physiological Processes through the Binding of Hormones to Receptors 1- Aminoacid Derivatives Classes of Hormones 2- Peptide Hormones 3- Lipid Derivatives 1- Aminoacid Derivatives They are hydrophilic, except thyroid hormones. Aminoacid • They are derived from amino acids and secreted by adrenal, pineal, and thyroid gland. Thyroid gland: Thyroxine (T4), Triiodothyronine (T3) Hydrophobic Hydrophobic Hydrophilic Adrenal glands: Epinephrine, Norepinephrine Pineal gland: Melatonin

8. 2- Peptide Hormones • They are chains of amino acids. They are hydrophilic. Peptide hormones are secreted by: Hypothalamus 1- Thyroid-stimulating hormone (TSH) 2- Luteinizing hormone (LH) 3- Follicle stimulating hormone (FSH) 4- Adrenocorticotropic hormone (ACTH) 5- Grow hormone (GH) 6- Prolactin (PRL) 7- Melanocyte stimulating hormone (MSH) 1- Adenohypophysis Regulatory hormones Oxytocin, ADH 1- Regulatory hormones 2- Oxytocin 3- Antidiuretic hormone (ADH) Neuro-hypophysis Adeno-hypophysis 2- Hypothalamus 3- Thyroid gland: Calcitonin 4- Parathyroid glands: Parathyroid hormone (PTH) TSH, LH, FSH, ACTH, GH, PRL, MSH Oxytocin, ADH 5- Pancreas: Insulin and Glucagon

9. 3- Lipid Derivatives They are hydrophobic. 1- Eicosanoids: Leukotrienes, Prostaglandins, Prostacyclins, and Thromboxanes They are derivatives of the arachidonic acid Leukotriene B4 2- Steroids: Sex hormones, Corticosteroids, and Calcitriol They are structurally similar to cholesterol Mineralocorticoids Glucocorticoids Androgens Androgens Estrogens Progestins 2- Suprarenal cortex: 1- Gonads: Aldosterone (mineralocorticoid) 3- Kidneys: Cholesterol Testosterone (androgen) Prednisone Estradiol (estrogen) (synthetic glucocorticoid) Cortisol (glucocorticoid) Calcitriol

11. Mechanisms of Hormone Action Hormones stimulate only those cells that have receptors for them. Receptors are protein or glycoprotein molecules on plasma membrane, in the cytoplasm, or inside the nucleus. Receptors act like switches turning on metabolic pathways when hormone binds to them. Metabolic effects can be achieved by different mechanisms: 1- Binding to intracellular receptors and activation of genes in the nucleus to initiate the transcription and synthesis of some proteins. 2- Binding to membrane receptors and activation of intracellular enzymes. cAMP Cyclic AMP (second messenger) Hydrophobic hormones: - Steroid hormones -Thyroid hormones Protein kinase Protein kinase (Active) (Inactive) Opens ion channels Activates other enzymes Hydrophilic hormones: - Aminoacid derivatives - Peptide hormones

12. Steroid hormone Thyroid hormone Cell membrane Target cell response Alteration of cellular structure activity CYTOPLASM Receptor Receptor Nuclear pore Nuclear envelope

13. 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 Hormone Hormone They are glycoproteins of the plasma membrane that bind specific hormones and determine the cell’s hormonal sensitivity. Receptor (beta) Receptor alpha 2 G protein G protein (activated) (active) G protein G protein G protein (inactive) (activated) 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 PDE PDE Adenyl cyclase Adenylate cyclase PDE Receptor (activated) (inactive) (activated) (inactive) (inactive) AMP ATP cAMP cAMP cAMP Protein kinase Enhanced breakdown of cAMP by Phosphodiesterase (PDE) 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 Reduction in cAMP leads to reduced enzyme activity They are enzymes that perform phosphorylations that activates or inactivates other enzymes It is an enzyme that inactivates cyclic AMP by converting it to AMP

14. EFFECTS ON Ca2+LEVELS Hydrophilic hormones A hormone binds to its receptor, which activates a G protein. 10 2 3 9 1 6 7 8 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 may bind to other gated membrane channels and alter the membrane potential of the cells. Calcium is a SecondMessenger that can have three effects: Calcium may activate cytoplasmic enzymes that alter cell metabolism. Calcium may bind to the protein Cadmodulin, which activates a protein kinase.

16. Hydrophobic Hormones (Steroids and Thyroid hormones) Hydrophilic Hormones (Peptides and Catecholamines) • 1- They penetrate plasma membrane and enter nucleus. • 1- They cannot penetrate into target cell. • 2- It takes several hours to days to show effect due to lag for protein synthesis. • 2- It takes minutes to hours to show effect. • 3- They act directly on the genes changing target cell physiology. • 3- They must stimulate target cell physiology indirectly: • a- Effects on cAMP levels (by activation of Adenylatecyclase) • b- Effects on Ca2+ levels through Inositol triphosphate (by activation of Phospholipase C)