Chapter 1--Introduction 1-1

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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 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
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