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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– 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
§ Endocrine System Components
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
Nucleosome
Linker DNA
Core particle
DNA windsaround coreparticles
11 nm
Interphase nucleus
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
Slide 30
1. Rough ER2. Smooth ER
Transport vesicles
Golgi complex
Plasma membrane
Secretory vesicles
3. Transport vesicle budding off
5. Secretory vesicle budding off
6. Secretion (exocytosis)
4. Fusion with Golgi complexTransport vesicle
1.3. Storage and Secretion
1-31
§ Storage and secretion1. 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 blood1. 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 degradation1. 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 action1. 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
§ Specificity1. 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. x43
Slide 44
Endocrinegland
Hormone
Binding with receptor
(Target cell)Binding of hormone with receptor triggers one of the following intracellular events:
Physiologicresponse
1. Alters channel permeability by acting on pre-existing channel-forming proteins and/or2. Acts through second-messenger system to alter activity of pre-existing proteins and/or3. Activates specific genes to cause formation of new proteins
A general hormone
elicits responses
Slide 45
Tubularlumenfiltrate Distal tubular cell
Peritubularcapillaryplasma
Waterchannel
Increases permeability ofluminal membrane to H2Oby inserting newwater channels
2 2
3
4 6
7
8
9
10
5
HormonesADHTRHOTLHRHCatecholamines
KeyDAG DiacylglycerolG G proteinIP3 Inositol triphosphate
Protein kinase
Ca2+
Ca2+
G GG
IP3
IP3
IP3G
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DAG
Diacylglycerol (DAG) pathway
Hormone
ReceptorPhospho-
lipase
InactivePK
ActivatedPK
Variousmetabolic
effects
Enzyme
ActivatedPK Calmodulin
InactivePK
SmoothER
Phospho-lipase Receptor
HormoneIP3-gated Ca2+ channeI
Ca2+-gatedion channel
Inositol triphosphate (IP3) pathway
PK
46
Slide 47
Firstmessenger, anextracellularchemicalmessenger
G proteinintermediary
Plasmamembrane
ECF
Receptor
(Binding of extracellularmessenger to receptoractivates a G protein, the subunit of which shuttlesto and activates adenylylcyclase)
(Converts)
(Activates)
(Phosphorylates)
(Phosphorylation inducesprotein to change shape)
Second messenger
= phosphate
ICFAdenylylcyclase
1.6. Mechanism of action—
B.Steroid hormones–
Fig. y
48
Slide 49
Plasmamembrane
Cytoplasm of target cell Nucleus
H = Free lipophilic hormoneR = Lipophilic hormone receptor
HRE = Hormone response elementmRNA = Messenger RNA
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)
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(▬)
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§ Negative feedback-2
1. Examples– Glucagon and Insulin
– Glucagon (alpha cells) of pancreas
– Insulin (beta cells) of pancreas
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§ 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
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§ Positive feedback—23. 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)
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