Chapter 1--Introduction

1. Chapter 1--Introduction

2. Ch. 1-- Study Guide Critically read: pp. 1-10 before Characteristics of Receptorssection skip pp. 11-20, read Regulation of Hormone Secretion (pp.21-23) Comprehend Terminology (the text in bold/italic) Study and understand the text and corresponding figures.

3. 1.1. Overview of the Endocrine System

4. § Homeostasis • Def. Internal environment be maintained constant within narrow ranges. • How? Communication among all cells using nervous + endocrine systems etc..

5. § Overview of Cell Communications • Necessary for integration of cell activities • Mechanisms • gap junctions; Figure x • pores in cell membrane allow signaling chemicals to move from cell to cell; Example-- • Neurotransmitters • released from neurons to travel across gap to 2nd cell; Examples-- • Local hormones; Figure 1 • secreted into tissue fluids to affect nearby cells by _____ • Paracrine; Autocrine– upon themselves; Juxtacrine • Hormones (strict definition)– Figure y • chemical messengers (small amount) that travel in the bloodstream . . . • Endocrine; Endocrine gland

6. Figure x– A neuron has a long fiber that delivers its neurotransmitter.

8. Figure y– Endocrine cells secrete a hormone into the bloodstream.

9. § Endocrine vs. Exocrine Glands • Exocrine glands • ducts carry secretion to a surface or organ cavity • extracellular effects (food digestion) • Example-- • Endocrine glands • no ducts; • intracellular effects, alter target cell metabolism • Example

10. § Endocrine System Components • Endocrine system • endocrine organs (thyroid, pineal, etc.) • hormone producing cells in organs (brain, heart and small intestine) • Endocrine glands (Figure z) • produce hormones • Hormone & neurohormone • chemical messenger secreted into bloodstream, stimulates response in another tissue or organ; How? • Target cells (Figure 1.2) • have receptors for a specific hormone

12. Fig. z--Endocrine glands

13. Endocrine glands in the text (Table 1.1) Classical endocrine glands– pituitary gland, thyroid gland, parathyroid gland, pancreas, adrenal glands, gonads, placenta. Organs with endocrine functions– brain, heart, liver, GI tract, kidneys, fat etc..

14. Goals and Objectives (p. 4) • The students should be familiar with essential features of feedback regulation • For each hormone, the student should know: • Its cell of origin • Its chemical nature • Its principal physiological actions • What signals or perturbations in the internal or external environment evoke or suppress its secretion

15. 1.2. Biosynthesis of Hormones

16. § Classification of hormones • Amines (tyrosine derivatives; epinephrine, NE)— • Steroid hormones– • Peptide/protein hormones– examples? • Examples Fig. x

18. § Synthesis of protein/peptide hormones • The amino acid sequence of proteins is encoded in the nucleotide sequence of DNA • DNA is organized into nucleosomes– nucleotides with histone molecules Fig. x + Fig. 1.3

19. § DNA Structure Space-filling model “Twisted ladder”

20. FIGURE 1.3—One strand of DNA

21. Interphase nucleus Core particle Linker DNA 11 nm DNA winds around core particles Nucleosome

22. Fig. 1.4--Complementary base pairing

23. § Synthesis of protein/peptide hormones (continued) • Transcription– introns are clipped out (Fig. 1.5 + 1.6)

24. FIGURE 1.5– Transcription and RNA processing

25. FIGURE 1.6—Alternative splicing

26. § Synthesis of protein/peptide hormones (continued) • Translation— (Fig. 1.7, 1.8 + x & y) • In what organelle are they made? • Storage or not?

28. FIGURE 1.7--Translation

29. FIGURE 1.8—Post translational processing

30. 1. Rough ER 2. Smooth ER 3. Transport vesicle budding off Transport vesicles 4. Fusion with Golgi complex Transport vesicle 5. Secretory vesicle budding off Golgi complex Secretory vesicles Plasma membrane 6. Secretion (exocytosis)

31. 1.3. Storage and Secretion

32. § Storage and secretion 1. For peptide hormones and tyrosine derivatives— Stored as __________ 2. Steps— (Fig. 1.9) • Recruitment • Docking to mem loci (by SNARE proteins; (Soluble NSF, N-ethylmaleimide-sensitive, Attachment Protein REceptor proteins) • Priming • Fusion with cell mem • Retrieval of the vesicular mem

33. FIGURE 1.9--Exocytosis

34. § Storage and secretion (continued) 3. For steroid hormones, For examples-- • Little storage • They diffuse across the cell mem as readily as they are produced.

35. 1.4. Hormones in Blood

36. § Hormones in blood • Many hormones bind to proteins – • Advantages– slow down degradation • Metabolic clearance rate– time needed for its concentration to be reduced by half • Where are these proteins produced? • Free hormones can pass through blood capillaries. (Fig. 10)

37. FIGURE 1.10—Hormones binding to protein

38. 1.5. Hormone Degradation

39. § hormone degradation • Just as important as secretion • Where? • In blood, intercellular spaces, in liver, kidney cells, and the target cells themselves • Often involves endocytosis--

40. 1.6. Mechanisms of Hormone Action

41. § hormone action • Hormonal messages must be converted to intracellular events; this is called signal transduction. • The series of biochemical changes above that are set in motion are described as signaling pathways.

42. § Specificity • Def.– All cells must be exposed to all hormones; however, cells respond only to their appropriate and specific hormones. • How? Receptors in the target cells • Details– a hormone receptor as a molecule in or on a cell that binds its hormone with great selectivity. This binding initiates response(s).

43. 1.6. Mechanism of action— • Peptide hormones– • Ex. Vasopressin (ADH-antidiuretic hormone) Fig. x

44. Endocrine gland A general hormone elicits responses Hormone Binding with receptor (Target cell) Binding of hormone with receptor triggers one of the following intracellular events: 1. Alters channel permeability by acting on pre-existing channel-forming proteins and/or 2. Acts through second-messenger system to alter activity of pre-existing proteins and/or 3. Activates specific genes to cause formation of new proteins Physiologic response

45. Peritubular capillary plasma Tubular lumen filtrate Distal tubular cell Increases permeability of luminal membrane to H2O by inserting new water channels Water channel

46. Inositol triphosphate (IP3) pathway Diacylglycerol (DAG) pathway Ca2+-gated ion channel Ca2+ Hormone Hormone IP3-gated Ca2+ channeI 1 1 Phospho- lipase Phospho- lipase Receptor Receptor 3 DAG IP3 G G G G 4 6 2 2 8 Inactive PK Activated PK 5 IP3 Ca2+ 9 Enzyme 7 Various metabolic effects IP3 10 Activated PK Calmodulin Smooth ER Inactive PK Hormones Key ADH DAG Diacylglycerol TRH G G protein OT IP3 Inositol triphosphate LHRH PK Protein kinase Catecholamines 46

47. First messenger, an extracellular chemical messenger Plasma membrane G protein intermediary ECF Adenylyl cyclase ICF (Converts) Receptor Second messenger (Binding of extracellular messenger to receptor activates a G protein, the a subunit of which shuttles to and activates adenylyl cyclase) (Activates) (Phosphorylates) (Phosphorylation induces protein to change shape) = phosphate

48. 1.6. Mechanism of action— • Steroid hormones– Fig. y

49. Plasma membrane Cytoplasm of target cell Nucleus      H = Free lipophilic hormone R = Lipophilic hormone receptor HRE = Hormone response element mRNA = Messenger RNA

50. 1.7. Regulation of Hormone Secretion