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Hormones and Cell Signaling

Hormones and Cell Signaling. Cellular Communication. Everything an animal does involves communication among cells e.g., moving, digesting food Cell signaling – communication between cells Signaling cell : sends a signal (usually chemical ) Target cell : receives the signal.

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Hormones and Cell Signaling

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  1. Hormones and Cell Signaling

  2. Cellular Communication • Everything an animal does involves communication among cells • e.g., moving, digesting food • Cell signaling – communication between cells • Signaling cell: sends a signal (usually chemical) • Target cell: receives the signal

  3. Types of Cell Signaling • Direct: via gap junctions • Indirect: signaling cell releases a chemical messenger that binds to a receptor on the target cell and activates a signal transduction pathway • Short distances • Paracrine: diffusion to a nearby cell • Autocrine: diffusion back to the signaling cell • Long distances • Endocrine: hormone is transported by the circulatory system • Neural: electrical signal travels along a neuron and releases a neurotransmitter

  4. Types of Cell Signaling

  5. Chemical Messengers • Two main types • Hydrophilic • Hydrophobic

  6. Direct Signaling • Gap junctions – specialized protein complexes that create an aqueous pore between two adjacent cells • Hydrophilic chemical messengers can travel through the lipid membrane • Typically involves the movement of ions Figure 4.2

  7. Indirect Signaling • Three steps • Release of chemical messenger from the signaling cell • Transport of the messenger through the extracellular environment to the target cell • Communication of the signal to the target cell

  8. Release of the Chemical Messenger • Hydrophobic messengers can cross the cell membrane by diffusion • Hydrophilic messengers are packed into vesicles where they are stored until they are released by exocytosis • Exocytosis – vesicle fuses with the plasma membrane and releases its contents

  9. Transport to the Target Cell • Hydrophilicmessengers dissolve in aqueous solutions like extracellular fluid and blood • Hydrophobicmessengers bind to carrier proteins in the blood • Carrier protein – help hydrophobic messengers dissolve in aqueous solutions • M + C  M-C

  10. Transport of Hydrophobic Messengers

  11. Communication to the Target Cell • Receptors • Hydrophilic: transmembrane protein • Hydrophobic: intracellular proteins • Ligand – chemical messenger that can bind to a specific receptor • The receptor changes shape when it binds to the receptor

  12. Ligand-Receptor Interactions • Only the correctly shaped ligand (natural ligand) can bind to the receptor • Ligand mimics (e.g., drugs and poisons) • Agonists – activate receptors • Antagonists – block receptors

  13. Ligand-Receptor Dynamics • L + R  L-R  response • More free ligand (L) or receptors (R) will increase the response • Receptors can become saturated

  14. Ligand-Receptor Dynamics, Cont. • More receptors   response • Higher affinity constant (Ka)   response • Down-regulation – constant exposure to ligands decrease the number of receptors, e.g., habitual coffee drinkers (mmmmmhhh) • Up-regulation – opposite, e.g., alcohol withdrawal

  15. Signal Transduction Pathways • Convert the change in shape of a receptor-ligand into a complex intracellular response

  16. Transducers • Convert signals from one form to another • Four components • Receiver: ligand binding receptor • Transducer: conformational change of the receptor • Amplifier: the signal transduction pathway increases the number of molecules affected • Responder: something that responds to the signal Figure 4.9

  17. Types of Receptors

  18. Intracellular Receptors • Regulate the transcription of target genes by binding to specific DNA sequences, and increasing or decreasing mRNA production

  19. Ligand-Gated Ion Channels • Ligand binds to receptor • Receptor changes shape opening a channel • Ions move across the membrane • Concentration and electrical gradients dictate the direction of ion movement • Movement of ions change ion concentrations which alters the membrane potential

  20. Receptor Enzymes • When activated by a ligand the catalytic domain starts a phosphorylation cascade • Named based on the reaction catalyzed

  21. G-Protein-Coupled Receptors • Transmembrane protein that interacts with intracellular G-proteins • G-proteins – named for their ability to bind guanosine nucleotides • Activate second messengers

  22. Second Messengers

  23. Systems for Cell Signaling

  24. Autocrine and Paracrine • Many chemicals act as paracrine messengers • Eicosanoids – act only in autocrine and paracrine cell signaling • Prostaglandins – involved in pain reception; blocked by many painkillers

  25. Nervous System • Specialized collection of cells that can carry signals across long distances • Neurons allow electrical signals to be propagated across long distances within a single cell • Synapse – region in between two neurons or a neuron and other target cells • Gap junctions • Chemical: neurotransmitters

  26. Endocrine System • Sends chemicals (hormones) through the blood • Produced by endocrine glands • Other chemicals can act as hormones, e.g., neurohormones • Non-endocrine organs can produce hormones, e.g., heart • Three types of hormones • Peptides • Steroids • Amines

  27. Three Types of Hormones Table 4.4

  28. Peptide Hormones • Synthesized on the rough ER • Stored in vesicles • Leave signaling cell via exocytosis • Soluble in aqueous solutions and travel to the target cell dissolved in the extracellular fluid • Hydrophilic: cannot cross the target cell membrane • Bind to transmembrane receptors • Rapid effects on the target cell

  29. Synthesis of Peptide Hormones Figure 4.23

  30. Steroid Hormones • Derived from cholesterol • Hydrophobic: can pass through the plasma membrane • Enzymes for synthesis are in the smooth ER or mitochondria • Cannot be stored within the cell

  31. Steroid Hormones, Cont. • Must be synthesized on demand • Transported to target cell by carrier proteins (e.g., albumin) • Sloooooow effects on the target cell (regulate transcription) – exception: stress hormone cortisol has rapid non-genomic effects

  32. Three Classes of Steroid Hormones • Mineralocorticoids • Electrolyte balance • e.g., aldosterone • Glucocorticoids • Stress hormones • e.g., cortisol • Reproductive hormones • Regulate sex-specific characteristics and reproduction • e.g., estrogen, progesterone, testosterone

  33. Amine Hormones • Chemicals that possess amine (-NH2) • e.g., acetylcholine, catecholamines (dopamine, norepinephrine, epinephrine), serotonin, melatonin, histamine, thyroid hormones • Some are true hormones, some are neurotransmitters, some are both • Diverse effects

  34. Exocrine Cell Signaling • Secretions via ducts to the outside of the body including the skin, respiratory surfaces, and the gut • e.g., salivary glands, prostate, sweat glands • Cell-to-cell: pheromones, allelochemicals

  35. Regulation of Cell Signaling • Feedback • Positive – output acts as a further stimulus • Negative – output reduces the stimulus

  36. Regulation of Cell Signaling, Cont.

  37. Direct Endocrine Pathways • Simplest system • Endocrine organ acts as the receptor, the integrating center, and the endocrine organ • e.g., parathyroid hormone

  38. Second Order Endocrine Pathways • Epinephrine – “fight-or-flight” response • Sense organ perceives and alarming stimulus • Sensory nerves send signals to the brain • Brain integrates the signals and sends signal out via the motor nerves • Adrenal medulla responds to this signal by releasing epinephrine • Epinephrine interacts with the heart and muscles

  39. Simultaneous Response Pathways • Insulin is part of a direct stimulus-response pathway and a second-order pathway

  40. Pituitary Hormones • The pituitary gland secretes many hormones • Two distinct sections • Anterior pituitary • Posterior pituitary

  41. Posterior Pituitary • Extension of the hypothalamus • Neurons that originate in the hypothalamus terminate in the posterior pituitary • Cell bodies synthesize neurohormones that travel in vesicles down the axons • e.g., Oxytocin and vasopressin • First-order endocrine pathway

  42. Anterior Pituitary • Hypothalamus synthesizes and secretes neurohormones •  • Portal system •  • Anterior pituitary • Tropic hormones – cause the release of another hormone • Third-order endocrine pathway

  43. Regulation of Blood Glucose • Very tightly controlled • Too low brain cannot function • Too high  osmotic balance of the blood is disturbed • Hormones: insulin and glucagon • Antagonistic pairing – hormones have opposite effects

  44. Evolution of Cell Signaling • Mechanisms for cell signaling share many similarities in all animal groups • Must have originated in a common ancestor

  45. Unicellular Organisms • Can sense and respond to their environment • Use mechanisms similar to cell signaling in animals • Examples • Motile bacteria: sense and move towards chemoattractants using transmembrane receptor proteins • Yeast: secrete mating factor pheromones that bind only to receptors on cells of the opposite mating type • Slime molds: free-living amoeboid organisms that form multicellular colonies; secrete cAMP to attract other cells that have specific receptors for cAMP

  46. Plants vs. Animals • Pathways have similar outlines, but different details • Similarities • Use Ca2+ as a secondary messenger • Have many pathways that involve protein kinases • Differences • Plants do not have receptor tyrosine kinases or Ras proteins • Plants have unique transmembrane serine/threonine kinases

  47. Vertebrates vs. Invertebrates • All have nervous systems; except sponges • Circulatory systems arose independently in several groups, e.g., arthropods and vertebrates • Endocrine systems could only arise in groups with circulatory systems and therefore also arose independently • All vertebrates use a series of steroid hormones, e.g., estrogens, androgens, and corticosteroids • Only estrogen has been found in invertebrates • Insects and crustaceans use a different series of steroids (e.g., ecdysone) to regulate molting and metamorphosis

  48. Vertebrate Hormones • Alterations in the way tissues respond to a hormone, rather than a change in the hormones • Similarities • Many hormones are affective across many groups, e.g., human growth hormone increase growth rate in fish, estrogen from pregnant mares are used in menopausal women • Differences • Prolactin stimulates milk production in mammals, inhibits metamorphosis and promotes growth in amphibians, and regulates water balance in fish

  49. Vertebrate Endocrine Organ Structure • Adrenal glands • The location of interrenal and chromaffin tissue differ across groups

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