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THE ENDOCRINE SYSTEM D. C. MIKULECKY PROFESSOR OF PHYSIOLOGY AND FACULTY MENTORING PROGRAM COMPARISON OF ENDOCRINE AND NERVOUS SYSTEMS • NERVOUS SYSTEM • “WIRED” • CHEMICAL SIGNAL AT TARGET CELL • RAPID • BRIEF DURATION • CLOSE ANATOMICAL PROXIMITY • ENDOCRINE SYSTEM • “WIRELESS” • CHEMICAL SIGNAL AT TARGET CELL • SLOW • LONG DURATION • SPECIFIC RECEPTORS WHAT IS A SIGNAL? • • • • • • • • SEMIOTICS INFORMATION THEORY NERVOUS SYTEM ENDOCRINE PARACRINE ENDOCRINE ANTIBODIES AND OTHER FOREIGN SUBSTANCES PARALLEL PROCESSING CHEMICAL SIGNALS • SIGNALING MOLECULE IS SECRETED • TRAVELS FRON ONE SITE TO ANOTHER • RECEPTOR AT TARGET • BINDING TO RECEPTOR EFFECTS SOME CHANGE ELEMENTS OF CELL SIGNALLING MECHANISMS • SIGNAL MOLECULES • RECEPTORS • SIGNAL TRANSDUCTION SIGNAL MOLECULES (FIRST MESSENGERS) • NEUROTRANSMITTERS • HORMONES • LOCAL MEDIATORS EXAMPLES OF SIGNALLING MOLECULES TYPE OF MOLECULE LOCAL MEDIATOR NEUROTRANSMITTER HORMONE PEPTIDES --- NEUROPEPTIDES VASOPRESSIN POLYPEPTIDES --- --- INSULIN AMINO ACIDS AND DERIVATIVES HISTAMINE GLYCINE EPINEPHRINE FATTY ACID DERIVATIVES PROSTAGLANDINS --- TESTOSTERONE OTHER SMALL MOLECULES --- ACETYLCHOLINE --- (SEE TABLE 1 IN TEXT) RECEPTORS • CELL MEMBRANE: HYDROPHILIC SIGNAL MOLECULES (POLYPEPTIDES, CATECHOLAMINES) • CYTOPLASMIC: HYDROPHOBIC SIGNAL MOLECULES (STEROIDS, VITAMIN D, THYROID HORMONE*) *BOUND TO CARRIER PROTEIN LIGANDS, AGONISTS AND ANTAGONISTS • LIGANDS BIND TO RECEPTORS IN A SPECIFIC MANNER • LIGANDS THAT ELICIT A PHYSIOLOGICAL RESPONSE ARE AGONISTS • LIGANDS THAT OCCUPY THE RECEPTOR BUT ELICIT NO RESPONSE ARE ANTAGONISTS (OR “BLOCKERS”) EXAMPLES OF ANTAGONISTS • PROPRANOLOL BLOCKS THE EFFECTS OF CATECHOLAMINES BY BINDING TO THEIR RECEPTORS • SPIRONOLACTONE BLOCKS ALDOSTERONE (DIURETIC) REGULATION OF RECEPTOR QUANTITY AS A CONTROL MECHANISM • DESENSITIZATION BY DOWNREGULATION DUE TO INCREASED ANTAGONIST LEVELS • INTERNALIZATION OF COMPLEX BY ENDOCYTOSIS • RECEPTOR SYNTHESIS (UPREGULATION) AN EXAMPLE OF RECEPTOR RECYCLING MEMBRANE RECEPTORS G-PROTEIN RECEPTOR SUPERFAMILY • MORE THAN 250 MEMBERS • SERPENTINE GLYCOPROTEINS LOOP BACK AND FORTH THROUGH MEMBRANE • EXTRACELLULAR DOMAIN: AMINO TERMINAL PEPTIDE AND THREE LOOPS (HYDROPHILIC REGIONS) • IN THE MEMBRANE:SEVEN ALPHA HELICES OF ABOUT 25 HYDROPHOBIC AA • SEE FIG 8 IN TEXT CATEGORIES OF HORMONES • PEPTIDES • AMINES • STEROIDS PEPTIDES • • • • HYDROPHILIC DISSOLVED IN PLASMA RECEPTOR ON CELL SURFACE cAMP OR CALCIUM AS SECOND MESSENGERS • ACTIVATE SPECIFIC GENES TO INITIATE PROTEIN SYNTHESIS PEPTIDE HORMONES • • • • • • • • HYPOTHALAMIC PITUITARY PANREATIC PARATHYROID GI KIDNEY LIVER HEART AMINES • THYROID HORMONE • CATECHOLAMINES • ALL DERIVED FROM AMINO ACID TYROSINE • UNIQUE SYNTHETIC AND SECRETORY PATHWAYS STEROIDS • LIPOPHILIC • RECEPTOR IN CYTOPLASM • ACTIVATE SPECIFIC GENES TO INITIATE PROTEIN SYNTHESIS • ADRENAL CORTICAL • GONADAL • PLACENTAL PLASMA CONCENTRATION OF HORMONES • • • • DEPENDS ON RATE OF SECRETION NEGATIVE FEEDBACK NEUROENDOCRINE REFLEXES DIURNAL RHYTHMS TYPES OF ENDOCRINE DISORDERS • HORMONE EXCESS • HORMONE DEFICIENCY • DECREASED RESPOSIVENESS OF RECEPTORS HYPOTHALAMUS AND POSTERIOR PITUITARY NEUROSECRETORY NEURONS VASOPRESSIN OXYTOCIN ANTERIOR PITUITARY HYPOTHALAMUS POSTERIOR PITUITARY SYSTEMIC ARTERY SYSTEMIC VEIN HYPOTHALAMUS AND ANTERIOR PITUITARY NEUROSECRETORY NEURONS ANTERIOR PITUITARY: •TSH •ACTH •PROLACTIN •GROWTH HORMONE •LH •FSH HYPOTHALAMUS POSTERIOR PITUITARY
