Chapter 1--Introduction

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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.

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1.1. Overview of the Endocrine System

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§ Homeostasis• Def. Internal environment be

maintained constant within narrow ranges.

• How? Communication among all cells using nervous + endocrine systems etc..

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§ 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.

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

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§ 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

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• 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

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Fig. z--Endocrine

glands

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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..

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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

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1.2. Biosynthesis of Hormones

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§ Classification of hormones

• Amines (tyrosine derivatives; epinephrine, NE)—

• Steroid hormones– • Peptide/protein hormones– examples?

• Examples

Fig. x 1-16

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§ 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

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§ DNA Structure

“Twisted ladder”Space-filling model 1-19

FIGURE 1.3—One strand of DNA

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Nucleosome

Linker DNA

Core particle

DNA windsaround coreparticles

11 nm

Interphase nucleus

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Fig. 1.4--Complementary base pairing

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§ Synthesis of protein/peptide hormones (continued)

1. Transcription– introns are clipped out (Fig. 1.5 + 1.6)

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FIGURE 1.5– Transcription and RNA processing

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FIGURE 1.6—Alternative splicing

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§ Synthesis of protein/peptide hormones (continued)

1.Translation— (Fig. 1.7, 1.8 + x & y)

–In what organelle are they made?

–Storage or not?

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FIGURE 1.7--Translation

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FIGURE 1.8—Post translational processing

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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

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§ 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

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§ Storage and secretion (continued)

3. For steroid hormones,

For examples--

– Little storage– They diffuse across the cell mem as

readily as they are produced.

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1.4. Hormones in Blood

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§ 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)

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FIGURE 1.10—Hormones binding to protein

1.5. Hormone Degradation

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§ 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--

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1.6. Mechanisms of Hormone Action

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§ 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.

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§ 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).

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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

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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

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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

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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

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§ 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

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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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