THE ENDOCRINE SYSTEM

2. THE ENDOCRINE SYSTEM D. C. MIKULECKY PROFESSOR OF PHYSIOLOGY AND FACULTY MENTORING PROGRAM

3. 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 COMPARISON OF ENDOCRINE AND NERVOUS SYSTEMS

4. WHAT IS A SIGNAL? • SEMIOTICS • INFORMATION THEORY • NERVOUS SYTEM • ENDOCRINE • PARACRINE • ENDOCRINE • ANTIBODIES AND OTHER FOREIGN SUBSTANCES • PARALLEL PROCESSING

5. CHEMICAL SIGNALS • SIGNALING MOLECULE IS SECRETED • TRAVELS FRON ONE SITE TO ANOTHER • RECEPTOR AT TARGET • BINDING TO RECEPTOR EFFECTS SOME CHANGE

6. ELEMENTS OF CELL SIGNALLING MECHANISMS • SIGNAL MOLECULES • RECEPTORS • SIGNAL TRANSDUCTION

7. SIGNAL MOLECULES (FIRST MESSENGERS) • NEUROTRANSMITTERS • HORMONES • LOCAL MEDIATORS

8. EXAMPLES OF SIGNALLING MOLECULES (SEE TABLE 1 IN TEXT)

9. RECEPTORS • CELL MEMBRANE: HYDROPHILIC SIGNAL MOLECULES (POLYPEPTIDES, CATECHOLAMINES) • CYTOPLASMIC: HYDROPHOBIC SIGNAL MOLECULES (STEROIDS, VITAMIN D, THYROID HORMONE*) *BOUND TO CARRIER PROTEIN

10. 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”)

11. EXAMPLES OF ANTAGONISTS • PROPRANOLOL BLOCKS THE EFFECTS OF CATECHOLAMINES BY BINDING TO THEIR RECEPTORS • SPIRONOLACTONE BLOCKS ALDOSTERONE (DIURETIC)

12. REGULATION OF RECEPTOR QUANTITY AS A CONTROL MECHANISM • DESENSITIZATION BY DOWNREGULATION DUE TO INCREASED ANTAGONIST LEVELS • INTERNALIZATION OF COMPLEX BY ENDOCYTOSIS • RECEPTOR SYNTHESIS (UPREGULATION)

13. AN EXAMPLE OF RECEPTOR RECYCLING

14. MEMBRANE RECEPTORSG-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

15. CATEGORIES OF HORMONES • PEPTIDES • AMINES • STEROIDS

16. PEPTIDES • HYDROPHILIC • DISSOLVED IN PLASMA • RECEPTOR ON CELL SURFACE • cAMP OR CALCIUM AS SECOND MESSENGERS • ACTIVATE SPECIFIC GENES TO INITIATE PROTEIN SYNTHESIS

17. PEPTIDE HORMONES • HYPOTHALAMIC • PITUITARY • PANREATIC • PARATHYROID • GI • KIDNEY • LIVER • HEART

18. AMINES • THYROID HORMONE • CATECHOLAMINES • ALL DERIVED FROM AMINO ACID TYROSINE • UNIQUE SYNTHETIC AND SECRETORY PATHWAYS

19. STEROIDS • LIPOPHILIC • RECEPTOR IN CYTOPLASM • ACTIVATE SPECIFIC GENES TO INITIATE PROTEIN SYNTHESIS • ADRENAL CORTICAL • GONADAL • PLACENTAL

20. PLASMA CONCENTRATION OF HORMONES • DEPENDS ON RATE OF SECRETION • NEGATIVE FEEDBACK • NEUROENDOCRINE REFLEXES • DIURNAL RHYTHMS

21. TYPES OF ENDOCRINE DISORDERS • HORMONE EXCESS • HORMONE DEFICIENCY • DECREASED RESPOSIVENESS OF RECEPTORS

22. HYPOTHALAMUS AND POSTERIOR PITUITARY NEUROSECRETORY NEURONS HYPOTHALAMUS VASOPRESSIN POSTERIOR PITUITARY OXYTOCIN SYSTEMIC ARTERY ANTERIOR PITUITARY SYSTEMIC VEIN

23. HYPOTHALAMUS AND ANTERIOR PITUITARY NEUROSECRETORY NEURONS HYPOTHALAMUS • ANTERIOR • PITUITARY: • TSH • ACTH • PROLACTIN • GROWTH • HORMONE • LH • FSH POSTERIOR PITUITARY