Chapter 1--Introduction 1-1 Ch. 1-- Study Guide 1. Critically read: – pp. 1-10 before Characteristics of Receptors section – skip pp. 11-20, – read Regulation of Hormone Secretion (pp.21-23) 2. Comprehend Terminology (the text in bold/italic) 3. Study and understand the text and corresponding figures. 1-2 1.1. Overview of the Endocrine System 1-3 § Homeostasis • Def. Internal environment be maintained constant within narrow ranges. • How? Communication among all cells using nervous + endocrine systems etc.. 1-4 § 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 1-5 Figure x– A neuron has a long fiber that delivers its neurotransmitter. 1-6 1-7 Figure y– Endocrine cells secrete a hormone into the bloodstream. 1-8 § 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 1-9 § 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 1-10 1-11 Fig. z-Endocrine glands 1-12 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.. 1-13 Goals and Objectives (p. 4) 1. The students should be familiar with essential features of feedback regulation 2. 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 1-14 1.2. Biosynthesis of Hormones 1-15 § Classification of hormones • Amines (tyrosine derivatives; epinephrine, NE)— • Steroid hormones– • Peptide/protein hormones– examples? • Examples Fig. x 1-16 1-17 § Synthesis of protein/peptide hormones 1. The amino acid sequence of proteins is encoded in the nucleotide sequence of DNA 2. DNA is organized into nucleosomes– nucleotides with histone molecules Fig. x + Fig. 1.3 1-18 § DNA Structure “Twisted ladder” Space-filling model 1-19 FIGURE 1.3—One strand of DNA 1-20 Interphase nucleus Core particle Linker DNA Nucleosome 11 nm DNA winds around core particles 1-21 Fig. 1.4--Complementary base pairing 1-22 § Synthesis of protein/peptide hormones (continued) 1. Transcription– introns are clipped out (Fig. 1.5 + 1.6) 1-23 FIGURE 1.5– Transcription and RNA processing 1-24 FIGURE 1.6—Alternative splicing 1-25 § Synthesis of protein/peptide hormones (continued) 1.Translation— (Fig. 1.7, 1.8 + x & y) –In what organelle are they made? –Storage or not? 1-26 1-27 FIGURE 1.7--Translation 1-28 FIGURE 1.8—Post translational processing 1-29 1. Rough ER 2. Smooth ER 3. Transport vesicle budding off Transport vesicles Transport vesicle Golgi complex 4. Fusion with Golgi complex 5. Secretory vesicle budding off Secretory vesicles Plasma membrane 6. Secretion (exocytosis) Slide 30 1.3. Storage and Secretion 1-31 § 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 1-32 FIGURE 1.9--Exocytosis 1-33 § Storage and secretion (continued) 3. For steroid hormones, For examples-– Little storage – They diffuse across the cell mem as readily as they are produced. 1-34 1.4. Hormones in Blood 1-35 § Hormones in blood 1. Many hormones bind to proteins – 2. Advantages– slow down degradation 3. Metabolic clearance rate– time needed for its concentration to be reduced by half 4. Where are these proteins produced? 5. Free hormones can pass through blood capillaries. (Fig. 10) 1-36 FIGURE 1.10—Hormones binding to protein 1.5. Hormone Degradation 1-38 § hormone degradation 1. Just as important as secretion 2. Where? – In blood, intercellular spaces, in liver, kidney cells, and the target cells themselves – Often involves endocytosis-- 1-39 1.6. Mechanisms of Hormone Action 1-40 § hormone action 1. Hormonal messages must be converted to intracellular events; this is called signal transduction. 2. The series of biochemical changes above that are set in motion are described as signaling pathways. 1-41 § Specificity 1. Def.– All cells must be exposed to all hormones; however, cells respond only to their appropriate and specific hormones. 2. How? Receptors in the target cells 3. Details– a hormone receptor as a molecule in or on a cell that binds its hormone with great selectivity. This binding initiates response(s). 1-42 1.6. Mechanism of action— A.Peptide hormones– • Ex. Vasopressin (ADH-antidiuretic hormone) Fig. x 43 A general hormone elicits responses Endocrine gland 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 Slide 44 Tubular lumen filtrate Water channel Distal tubular cell Peritubular capillary plasma Increases permeability of luminal membrane to H2O by inserting new water channels Slide 45 Inositol triphosphate (IP3) pathway Diacylglycerol (DAG) pathway Ca2+-gated ion channel Hormone Ca2+ Hormone IP3-gated Ca2+ channeI 1 1 Receptor Phospholipase Phospholipase 3 2 DAG IP3 G G 4 Inactive PK Receptor Activated PK G G 6 2 8 5 IP 3 Ca2+ Enzyme 9 Various metabolic effects Key DAG G IP 3 PK IP3 10 Activated PK Hormones ADH TRH OT LHRH Catecholamines 7 Calmodulin Inactive PK Smooth ER Diacylglycerol G protein Inositol triphosphate Protein kinase 46 First messenger, an extracellular chemical messenger G protein intermediary Receptor (Binding of extracellular messenger to receptor activates a G protein, the a subunit of which shuttles to and activates adenylyl cyclase) (Converts) Plasma membrane ECF Adenylyl ICF cyclase Second messenger (Activates) (Phosphorylates) (Phosphorylation induces protein to change shape) = phosphate Slide 47 1.6. Mechanism of action— B.Steroid hormones– Fig. y 48 Plasma membrane Cytoplasm of target cell Nucleus H = Free lipophilic hormone R = Lipophilic hormone receptor HRE = Hormone response element mRNA = Messenger RNA Slide 49 1.7. Regulation of Hormone Secretion 1-50 § Negative feedback-1 1. Principle– Def. The body senses a change and activates mechanisms that negate (reverse) it; • (On pituitary hormones) target organ hormone levels inhibits release of tropic hormones 2. Example– TRH-TSH-thyroid hormones (see next slide; Fig. x, 1.25) 51 (▬) 52 53 § Negative feedback-2 1. Examples– Glucagon and Insulin – Glucagon (alpha cells) of pancreas – Insulin (beta cells) of pancreas 54 55 56 § Positive feedback—1 1. Definition– change in a factor triggers a physiological response that AMPLIFIES an initial change 2. Example— in the birth of a baby; how? Fig. y 57 Self-amplifying cycle 58 § Positive feedback—2 3. Details of birth of a baby – 1. Uterine contractions push the fetus against the cervix – 2. The stretching of the cervix (RECEPTOR/SENSOR is the nerve cells here) triggers nerve impulses to the brain – 3. Brings about oxytocin secretion – 4. The hormone oxytocin causes even STRONGER powerful contractions of the uterus (EFFECTOR is muscles in wall of uterus) 59