Cell Signaling and Endocrine Regulation

1. Cell Signaling and Endocrine Regulation

2. Myxobacteria (soil-dwelling bacteria)

3. Dictyostelium discoideum (cellular slime mold)

4. Vibrio fischeri (marine bioluminiscent bacterium) The Hawaiian bobtail squid (Eupryma scolopes) has a unique mutually beneficial (symbiotic) relationship with the bioluminescent bacterium Vibrio fischeri. (Image from M. J. McFall-Ngai and E. G. Ruby, University of Hawaii; National Science Foundation) Free-living Vibrio fischeri

5. Pheromonal communication in insects Tandem running of Procornitermes araujoi Emerson. • the male follows the large female, which acts as a leader in this process. The honey bee queen produces pheromones that help her: • attracting a retinue of workers around her, • attracting drones on mating flights, • preventing workers from reproducing at the individual (worker egg laying) and colony (swarming) level • regulating several other aspects of colony functioning.

6. Cellular Communication Signalling Cell Target Cell signal (Chemical messenger) Response • Everything an animal does involves communication among cells • Example: moving, digesting food • Cell signaling – communication between cells

7. Cell Signalling Indirect Direct Long Distance Short Distance

8. Gap Junction Figure 3.2

9. Indirect Signaling Table 3.1

10. Glands Figure 3.3

11. Chemical Messengers Chemical messengers Hydrophobic/ Lypophilic Hydrophilic Other Lipids Peptides Purines Amines Steroids Gases • Structure of chemical messenger (especially hydrophilic vs. hydrophobic) affects signaling mechanism

12. Indirect Signaling Table 3.2

13. Peptide Hormones - Synthesis & Secretion Figure 3.4

14. Synthesis & Secretion of AVP/ADH Figure 3.5

15. Botulinum toxin • a protein produced by the bacterium Clostridium botulinum • affects the regulated exocytosis of neurotransmitters, preventing muscles contraction.

16. Transmembrane Receptor Figure 3.6

17. Steroid Hormones Smooth ER Cholesterol Mitochondria Steroids Reproductive hormones Glucocorticoides Mineralocorticoids Electrolyte balance Stress hormones Sex-specific characteristics

18. Steroid Hormones • Hydrophobic • Can diffuse through plasma membrane • Cannot be stored in the cell • Must be synthesized on demand • Transported to target cell by carrier proteins • Example: albumin • Bind to intracellular or transmembrane receptors • Slow effects on target cell (gene transcription) • Stress hormone cortisol has rapid non-genomic effects

19. Steroid Hormones Figure 3.8

20. Amine Hormones/ Biogenic Amines • Chemicals that possess amine group (–NH2) • Example: acetylcholine, catecholamines (dopamine, norepinephrine, epinephrine), serotonin, melatonin, histamine, thyroid hormones • Some true hormones, some neurotransmitters, some both • Most hydrophilic • Thyroid hormones are hydrophobic • Diverse effects

21. Other Chemical Messengers • Eicosanoids • Most act as paracrines • Hydrophobic • Often involved in inflammation and pain • Example: prostaglandins, leukotrienes • Gases • Most act as paracrines • Example: nitric oxide (NO), carbon monoxide • Purines • Function as neuromodulators and paracrines • Example: adenosine, AMP, ATP, GTP Figure 3.10

22. Communication to the Target Cell • Receptors on target cell • Hydrophilic messengers bind to transmembrane receptor • Hydrophobic messengers bind to intracellular receptors • Ligand • Chemical messenger that can bind to a specific receptor • Receptor changes shape when ligand binds

23. Ligand-Receptor Interactions • Ligand-receptor interactions are specific • Only the correctly shaped ligand (natural ligand) can bind to the receptor • Ligand mimics • Agonists – activate receptors • Antagonists – block receptors • Many ligand mimics act as drugs or poisons

24. Ligand-Receptor Interactions • A ligand may bind to more than one type of receptor • Receptor isoforms • Expressed on different target cells • Different responses to the same ligand • A single cell may have receptors for many different ligands

25. Ligand-Receptor Binding Figure 3.12

26. Changes in Number of Receptors • Number of receptors affects number of L-R complexes • More receptors   L-R complexes   response • Target cells can alter receptor number • Down-regulation • Target cell decreases the number of receptors • Often due to high concentration ligand • Up-regulation • Target cell increases the number of receptors

27. Changes in Number of Receptors Figure 3.13a

28. Ligand-Receptor Dynamics • Affinity of receptor for ligand affects number of L-R complexes • Higher affinity constant (Ka)   response Figure 3.13b

29. Inactivation of Ligand-Receptor Complex • L-R complex must be inactivated to allow responses to changing conditions Figure 3.14

30. Signal Transduction Pathways • Convert the change in receptor shape to an intracellular response • Four components • Receiver • Ligand binding region of receptor • Transducer • Conformational change of the receptor • Amplifier • Increase number of molecules affected by signal • Responder • Molecular functions that change in response to signal

31. Transduction Pathway Figure 3.15

32. Types of Receptors Figure 3.16

33. Intracellular Receptors Figure 3.17

34. Changes in Gene Transcription Figure 3.18

35. Ligand-Gated Ion Channels Figure 3.19

36. Receptor Enzymes Figure 3.20

37. G-Protein-Coupled Receptors Figure 3.25

38. Second Messengers Table 3.3

39. Inositol-Phospholipid Signaling Figure 3.26

40. Cyclic-AMP Signaling Figure 3.27

41. Interaction Among Transduction Pathways • Cells have receptors for different ligands • Different ligands activate different transduction pathways • Response of the cell depends upon the complex interaction of signaling pathways

42. Regulation of Cell Signaling Regulated variable Biological Control Systems Response Integrating center Signal Signal Sensor Effector • Cell signaling is important for regulation of physiological processes • Components of biological control systems:

43. Regulation of Cell Signaling • Set Point • The value of the variable that the body is trying to maintain • Feedback loops • Positive • Output of effector amplifies variable away from the set point • Positive feedback loops are not common in physiological systems • Negative • Output of effector brings variable back to the set point

44. Feedback Regulation Figure 3.28

45. Pituitary Hormones • Pituitary gland secretes many hormones • Two distinct anatomic sections: • Anterior pituitary (adenohypophysis) • Posterior pituitary (neurohypophysis)

46. Posterior Pituitary • Extension of the hypothalamus • Neurons that originate in hypothalamus terminate in posterior pituitary • Neurohormones oxytocin and vasopressin synthesized in cell body and travel in vesicles down axons • First-order endocrine pathway • Hypothalamus receives sensory input • Hypothalamus serves as integrating center

47. Posterior Pituitary Figure 3.29

48. Anterior Pituitary • Hypothalamus synthesizes and secretes neurohormones •  • Hypothalamic-pituitary portal system •  • Anterior pituitary releases hormones • Tropic hormones • Cause release of another hormone • Third-order endocrine pathway

49. Anterior Pituitary Figure 3.30

50. Hypothalamus and Anterior Pituitary Figure 3.31