Download Chapter 3-Thyroid Gland 3-1

Chapter 3-Thyroid Gland
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Ch. 3-- Study Guide
1. Critically read (1) pages pp. 43-50 before
Metabolism of thyroid hormones section; (2)
pages 56 (Regulation of thyroid hormone
section) to the end of the chapter
2. Comprehend Terminology (the text in
bold/italic)
3. Study and understand the text and
corresponding figures.
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3.1. Introduction
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§ Introduction
1. Thyroid hormone:
– required in every organ system
– Thyroid hormone acts as a
modulator
– It plays an indispensable role in
growth and development
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3.2. Morphology
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§ Morphology (1)
1. Location— right below the cricoid
cartilage
2. Gross anatomy– 3 lobes;
– Two large lateral lobes:
– One pyramidal lobe:
– Weight: 20g
– Goiter: several hundred grams
3. Receives a greater/lesser (select one)
flow of blood/lymph than most other
tissues of the body
4. Receives abundant nerves of ANS
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§ Morphology (2)
5. Histology— Fig. 3.2 + x
A. The functional unit: follicle– epithelial cells
(cuboidal or columnar) . . .—produces
thyroid hormones
B. Glycoprotein colloid, inside the follicle,
called thyroglobulin
C. A group of follicle forms a lobule
surrounded by connective tissue (septum)
D. Parafollicular cells, C cells (between
follicles– produce calcitonin
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A
C
D
B
1--Follicular cells; 2– colloid; 3– septum;
4– parafollicular cells
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3.3. Thyroid hormones
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§ Thyroid hormones
1. Structure--Amino acid derivatives
of tyrosine (Fig. 3.3)
– Thyroxine: more abundant
– Triiodothyronine: less abundant,
more potent
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3.3A. Biosynthesis of
Thyroid hormones
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§ Iodine trapping
1. Made possible by iodide pump:
– Sodium iodide symporter
– Energy needed
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§ Thyroglobulin synthesis
Steps of thyroglobulin movement:
1. Thyroglobulin (TG)– is a precursor of T3,
T4
2. Thyroglobulin is produced in the
ribosomes
3. TG is released into the follicular lumen.
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§ Incorporation of iodine
Iodide movement:
1.Diffusion throughout the follicular cell
2.Exit from the apical membrane by iodide
transporters called pendrin
3.(Organification) Oxidized form of iodides is
linked to thyroglobulin (TG) by
thyroperoxidase (TPO)
– This produces monoiodotyrosine (MIT)
and diiodotyrosine (DIT);
– (Coupling)--they may also become T3
and T4 pretty soon by TPO
Fig. 3.4 & 3.5
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Coupling
of MIT
and DIT
to T4
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§ Storage and secretion of thyroid hormones
1. (Storage)–
–
–
At follicular lumens
MIT and DIT in thyroglobulin comprise 90% of the
total pool of iodine in the body
2. (Secretion)– Endocytosis + exocytosis
–
–
(Endocytosis) TG is brought back into follicular cells
Long pseudopodia reach out from apical surfaces to
“scoop up” TG (Fig. 3.6)
– Endocytic vesicles migrate toward the basal
membrane + meet with lysosome
– (Exocytosis)– T4 and T3 (20:1) are released into the
bloodstream; MIT and DIT reused in the cell.
Fig. 3.4 again
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3.4. Control of thyroid
function
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§ Effects of TSH
1. The principal regulator of thyroid function is
the TSH (thyroid-stimulating hormone)
2. Pleiotropic physiology by TSH– on thyroid
hormone biosynthesis and secretion, and
increase blood flow to the thyroid.
3. (TSH receptors) TSH binds to G-proteincoupled receptors in ________ cells.
4. (Second messengers)– mainly through
cAMP followed by protein kinase A; but
also through diacylglycerol (DAG)/inositol3-24
trisphosphate (IP3)
§ Effects of thyroid-stimulating
immunoglobulins
1. Hyperthyroidism– overproduction of
thyroid hormone (Graves’ disease):
– Extremely low of TSH in blood plasma
– Yet the thyroid is under intense
stimulation; why? (see below)
– TSI (Thyroid-stimulating immunoglobulin)
from the lymphocytes can bind to TSH
receptors
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§ Autoregulation of thyroid
hormone synthesis
1. Thyroid hormone production is blocked
temporarily when the iodide in blood
plasma becomes too high
2. Thyroglobulin also down regulates
biosynthetic activity of the thyroid gland–
this action is through down regulation of
thyroglobulin, thyroid peroxidase, the
sodium iodide symporter, and the TSH
receptor
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3.5. Thyroid hormones in
blood
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§ Three binding proteins
1. 99% of thyroid hormones binds to the
following three proteins
A. Thyroxine-binding globulin (TBG)– binds to
@ 70% of the total protein-bound hormone;
why?
B. Transthyretin (TTR)—15%
C. Albumin—15%
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Hydrophilic Receptor in Target
hormone
plasma
cell
membrane
Transport
protein
Secondmessenger
activation
Free
hormones
Bound
hormone
Hydrophobic
hormone
Receptor in
Tissue fluid
nucleus
Blood
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TBG
T3
T4
Various
metabolic effects
Protein
synthesis
mRNA
DNA
T4
I
T3
Blood
Tissue fluid
Target cell
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3.6. Regulation of thyroid
hormone secretion
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§ Feedback mechanism of
thyroid hormones
1. No TSH– thyroid cells are atrophy
2. Administer of TSH– increases thyroid
hormones
3. Patients lack TSH receptors–
hypothyroidism, no functional thyroid
gland, and high levels of TSH
4. Feedback of thyroid hormones on both
TRH and on thyrotropes
Fig. 3.12 and 3.13
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In Thyrotrope:
--T3 on TRH
and TSH;
--TRH on TSH
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Thyroid hormones (3-4 weeks) reduce the
sensitivity of the thyrotropes to TRH
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3.7. Mechanism of thyroid
hormone action
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§ Mechanism of thyroid hormone action
1. All cells require optimal amounts of thyroid
hormone for normal operation
2. Thyroid hormone receptors are the nuclear
receptor; however not completely understood
3. Details–
–
–
Thyroid hormone receptors bind to the gene they
regulate no matter the hormone is present or not
Once binding T3, the configuration of the receptor is
modified; corepressor is released and binds to a
coactivator (Fig. 3.15)
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