Endocrine and Reproduction Systems PDF

1 Module (Endocrine and Reproduction Systems) Level 2 Semester 3 Module Code (EAR310)  Instructor information Contact: Prof Dr Adel Abdel Kader Zalata Department: Medical Biochemistry and Molecular Biology Official email: adel_zalata@yaho...

1 Module (Endocrine and Reproduction Systems) Level 2 Semester 3 Module Code (EAR310)  Instructor information Contact: Prof Dr Adel Abdel Kader Zalata Department: Medical Biochemistry and Molecular Biology Official email: [email protected]  2 Module (Endocrine and Reproduction Systems) Lecture 4 Hormones classification, Chemical structure and mode of Action Staff members of Medical Biochemistry Dept. Faculty of Medicine Delta University  3 Learning objectives By the end of the lecture, the students will be able to : 1. Define endocrine system & hormones. 2. Identify the site of hormonal action. 3. Explain the general functions of hormones. 4. Explain the different methods of Classification of Hormones.  Definitions 5 Hormones are: 1. Chemical messengers or regulators. 2. Produced by the endocrine system and secreted directly into the blood and distributed by circulatory system. 3. Released by cells in one part of the body and affect cells in other parts of the body. 4. They slow down or speed up chemical processes. Summary of Classification of Hormones 26  6 Site of Hormonal Action A. Hormones : act near to their site of release or at a distant organ in the body.  General functions of hormones: 8 A. Regulation of metabolism: of carbohydrate, protein, lipids and minerals, directing their synthesis, storage, mobilization and utilization according to needs. B. Growth: The growth of bones, viscera and various types of tissues is under the control of hormones. C. Homeostasis: Hormones help the maintenance of internal environment. D. Behaviour: Fear, depression and sex behaviour are due to several natural hormonal factors. E. Reproduction: Reproductive organs are highly sensitive to hormones.  9 Classification of Hormones  11 Classification According to Chemical Structure Hormones can be classified chemically into 3 main groups as follows: 1.Peptide/Protein Hormones 2.Amino Acid Derivatives 3.Steroid Hormones In addition to: Miscellaneous : (Eicosanoids & vitamins A & D)  13 1-Peptide/Protein Hormones The peptide hormones include: 1.Short polypeptide chains such as antidiuretic hormone and oxytocin produced in the brain and released into the blood in the posterior pituitary gland. 2.Small proteins, like growth hormones produced by the pituitary, and large glycoproteins such as follicle-stimulating hormone produced by the pituitary. 3.Secreted peptides like insulin are stored within vesicles in the cells that synthesize them. They are then released in response to stimuli such as high blood glucose levels in the case of insulin.  1. Peptide/Protein Hormones 14 4. Solubility: Amino acid-derived and polypeptide hormones are water-soluble and insoluble in lipids. 5. Receptors: These hormones cannot pass through plasma membranes of cells; therefore, their receptors are found on the surface of the target cells. Examples: Insulin, glucagon, calcitonin, pituitary hormones, and parathormone.  2. Amino Acid-Derived Hormones 15 1. Relatively small molecules hormones that are derived from the amino acids: tyrosine and tryptophan. 2. Their chemical name end with “-ine”. Examples include epinephrine and norepinephrine and thyroxine. 3. The pineal gland in the brain makes and secretes melatonin which regulates sleep cycles.  Examples: T3 and T4 hormones (thyroid hormones), adrenaline, and noradrenaline (catecholamines).  3. -Lipid-Derived Hormones (or Lipid-soluble 17 Hormones) 1. Most lipid hormones are derived from cholesterol and thus are structurally similar to it. 2. The steroid hormones. are derived from cholesterol. 3. Chemically, these hormones are usually ketones or alcohols; their chemical names end with “-ol” for alcohols or “-one” for ketones. Examples of steroid hormones include estradiol, which is an estrogen, or female sex hormone, and testosterone, which is an androgen, or male sex hormone. 4. Other steroid hormones include aldosterone and cortisol, which are released by the adrenal glands along with some other types of androgens.  18 3-Lipid-Derived Hormones (or Lipid- soluble Hormones) 6. Steroid hormones are insoluble in water. 7. They are transported by transport proteins in blood. 8. As a result, they remain in circulation longer than peptide hormones. 9. For example, cortisol has a half-life of 60 to 90 minutes, while epinephrine, an amino acid derived-hormone, has a half-life of approximately one minute. Examples: Adrenocorticosteroids, androgens, progesterone, andestrogens.  Classification of Hormones 20 Trophic & nontrophic 1. Trophic Hormones a. These hormones act on endocrine glands. They control growth of target endocrine gland. b. Examples: Anterior pituitary hormones (TSH controls proliferation of thyroid gland)  Classification of Hormones 21 Trophic & nontrophic 2. Non-trophic Hormones a. These hormones act directly on target cells and regulate cell functions. b. Examples: Insulin, glucagon, and thyroxin  Classification of Hormones 22 Mechanism of action Group I Group II Types Steroids, Polypeptides, iodothyronines, proteins, calcitriol, glycoproteins, retinoids catecholamines Hormones are Solubility Lipophilic Hydrophilic classified into Transport Yes No proteins group I & Plasma half life Long (hours to Short (minutes) days) group II. Receptors Intracellular Cell surface Mediator Receptor- cAMP, cGMP, hormone complex Ca2+, metabolites of complex phosphinositols, kinase cascades  23 Notes: 1. Vitamins A & D are considered hormones as they have hormonal like actions. 2. Eicosanoids: A. Are hormone-like compounds (e.g., prostaglandins, thromboxanes, and leukotrienes). B. They are important regulators of blood pressure, blood clotting, and the immune response.  Mode of action of hormone Hormone Receptors Def.: Specific protein which identify its agonist with high degree of specificity and sensitivity. Intracellular receptors A- Nuclear receptors e.g estrogens B- Cytoplasmic receptors e.g. Most steroid and thyroid hormones Cell surface membrane receptors e.g. Polypeptide hormones and catecholamines  6 Hormone Receptors 8 9 10 11 12 13 14 15 16 17 18  Mechanism of hormone Action There are 2 groups: I- Group I: Includes hormones that bind to the intracellular receptors. II- Group II: Includes hormones that bind to cell surface receptors.  21 Group I: that bind to intracellular receptors  Group I: Hormones that bind intracellular 22 receptors 1. The hormone diffuses through the cell membrane of the target cells and binds to specific receptors protein in the cytosol or the nucleus, forming a complex. 2. The hormone-receptor complex then undergoes activation reaction, which leads to change in size, conformation and surface charge of this complex, making it able to bind to DNA at specific region called “hormone response element “(HRE).  23 Group I: Hormones that bind intracellular receptors 3. The hormone-receptor complex in this position will activate or inactivate the promoter element; PE (which is a part of DNA that determines the initiation of the transcription). 4. This will affect the transcription of specific genes, and production of mRNA and protein molecules.  Group II: Hormones that 24 bind to cell surface receptors 1. A hormone (first messenger) binds to a specific receptor located in the cell membrane to activate a second messenger which located in the cytosol.  Group II: Hormones that 24 bind to cell surface receptors 2. The second messenger may be one of the following molecules: A. cyclic AMP (cAMP), B. cyclic GMP (cGMP), C. Calcium calmodulin, D. Inositol triphosphate, E. Diacylglycerol  25 Hormones use cAMP as the second cAMP: messenger: 1. If the second messenger is  26 c-AMP derived from ATP through the action of adenylate cyclase: adenylate cyclase is the second messenger for many hormones, e.g. epinephrine, glucagon, calcitonin, PTH. Hormones use cAMP as the second 27 messenger:  28 Hormones use cAMP as the second messenger: 1. Hormone binds to cell membrane receptors. This makes conformational changes of G-protein dissociating it into  subunit & exchanges GDP for GTP. 2. This activates adenylyl cyclase (AC) present at the inner surface of the cell membrane. 3. Then active adenylate cyclase will convert ATP into cAMP (second messenger) in the cytosol.  29 Hormones use cAMP as the second messenger: 4. Cyclic AMP will stimulate an enzyme called protein kinase. 5. This enzyme is composed of 4 subunits: 2 regulatory (R) and 2 catalytic (C). 6. The whole protein kinase is inactive but binding of cAMP with the enzyme dissociates R from C and activating it.  30 Hormones use cAMP as the second messenger: 7. catalytic subunits (C) responsible for the phosphorylation of several enzymes and transcription factors. 8. Phosphorylation alters activities of these enzymes, some get active (e.g. glycogen phosphorylase) while other get inactivated (e.g. glycogen synthase). 9. It also affects gene expression to mediate cell growth and differentiation Hormones use Phosphatidylinositol/calcium as the 31 second messenger Hormones use Phosphatidylinositol/calcium 33 as the second messenger: 1. Certain hormone binds to cell membrane receptors and result in the activation of phospholipase C (PLC). 2. PLC activate a specific G protein, and at the same time activate calcium channel allowing calcium to enter the cell. 3. phospholipase C (PLC) generates inositol triphosphate (IP3), which liberates stored intracellular Ca2+, and diacylglycerol (DAG) Hormones use Phosphatidylinositol/ 34 calcium as the second messenger: 4. DAG activates protein kinase C (PKC) which phosphorylate several proteins & enzymes. 5. The released calcium will activate specific protein called: calmodulin.  27 Questions 1. Endocrine glands differ from exocrine glands in that: A. Endocrine glands are ductless and exocrine glands release secretions at the body's surface or into ducts. B. Endocrine glands release hormones, whereas exocrine glands release waste. C. Endocrine glands are formed by epithelial tissue, but exocrine glands are primarily connective tissue. D. Endocrine glands are all interconnected; whereas exocrine glands act completely independently. E. Endocrine glands are all steroid in nature  28 Questions 2. Which of these is not an endocrine gland? A. Pancreas. B. Testes. C. Salivary gland. D. Ovaries. E. Parathyroid.  30 Questions 3. The chemical classification of hormones does NOT include: A. amino acid-based hormones B. glucose-containing hormones C. vitamin-containing hormones D. protein-based hormones E. steroid hormones  37 Questions 4-Hormone receptors are A. glycolipids B. lipids C. polysaccharides D. Proteins E. Lipoproteins 5- Steroid hormones receptor binds to A. Hormone response elements in m-RNA B. Hormone response elements in DNA C. Hormone response elements in proteins D. Ribosomes to stimulate translation E. Plasma membrane 6- A Mode of action of steroid hormones involve: 39 A. Stimulation of DNA replication B. Stimulation of m-RNA transcription C. Stimulation of translation D. Inhibition of protein synthesis E. Secondary messenger 7- Adenylate cyclase is activated by A- GDP-bearing -Subunit of G-protein B- GTP-bearing -Subunit of G-protein C- GDP-bearing -Subunit of G-protein D- GTP-bearing -Subunit of G-protein E- GTP-bearing -Subunit of G-protein 8- G-protein-coupled activation of phospholipase C 39 results in A- Activation of phosphodiesterase.B-inactivation of adenylate cyclase. C- Activation of protein kinase C. D- Decrease of inositol 1,4,5-trisphosphate (IP3). E- Increase of phosphatidylinositol 4,5-bisphosphate (PIP2). 9- Elevation of intracellular inositol triphosphate (IP3) results in the release of Ca2+ from which of the following organelles? A_ Peroxisomes B- Lysosomes C- Mitochondrion D- Nucleus E- Smooth endoplasmic reticulum  10- Cortisol crosses the membranes of all cells but affect 39 only target cells because: A- Only target cells retain the appropriate DNA segments B- Intracellular receptors are present only in target cells C- Most cells lack the Y chromosome required D- Only target cells possess the cytosolic enzymes that transduce the cortisol E- Only in target cells is cortisol able to initiate the phosphorylation cascade leading to activated transcription factor 11- Thyroid hormones, glucocorticoids and gonadal steroids are similar in that each: A- Is derived from cholesterol B- Is derived from amino acids C- Acts on only one target organ or tissue D- They have intracellular receptors E- Is released in response to signals from the hypothalamic- posterior pituitary complex Prof. Adel Zalata