Physiology Endocrine Thyroid Gland

Front 1

Thyroid hormone is a crucial determinant of in ______ ________ _________the body.

Back 1

growth and development, affecting nearly every tissue

Front 2

Thyroid hormone is a regulator of ?

Back 2

overall cellular energy expenditure and substrate utilization.

Front 3

Thyroid hormone serves to optimize the ?

Back 3

sensitivity of particular tissues to various other hormones and other factors.

Front 4

The lack or excess of thyroid hormone can have ?

Back 4

dramatic effects on the brain, bones, the cardiovascular system and whole body metabolism

Front 5

Follicular cells make
a precursor protein
of thyroid hormone,
called ??

Back 5

thyroglobulin.

Front 6

The iodinated form of
thyroglobulin
is stored in ?

Back 6

the colloid

Front 7

The thyroid hormones
are excised from __________
and
are release

Back 7

- thyroglobulin

- to the circulation.

Front 8

The Follicular Cell And Its
Role In T4 And T3 synthesis

Iodide (dietary) is activity transported, .....

Back 8

(with Na+)
into the cell; Requires ATP.

Front 9

The Follicular Cell And Its
Role In T4 And T3 synthesis

Thyroglobulin (MW~660 kd) is synthesized .....

Back 9

in the follicular cell.

Thyroglobulin is composed of many tyrosines

Front 10

The Follicular Cell And Its
Role In T4 And T3 synthesis

At the apical surface of the follicular cells, iodine

Back 10

is oxidized and attached to thyroglobulin
by a thyroid peroxidase, generating iodotyrosine.

Front 11

The Follicular Cell And Its
Role In T4 And T3 synthesis:

The iodotyrosines are coupled
to form

Back 11

iodothyronines.

Front 12

The Follicular Cell And Its
Role In T4 And T3 synthesis:

Thyroglobulin, with iodothyronines,is stored

Back 12

in the colloid.

This is a huge reservoir of hormone precursor.

Front 13

The Follicular Cell And Its
Role In T4 And T3 synthesis:

To get thyroid hormones
into the circulation,
thyroglobulin re-enters the cells by .....

Back 13

endocytosis.

Front 14

The Follicular Cell And Its
Role In T4 And T3 synthesis:

Thyroglobulin is degraded by
lysosomal enzymes to release

Back 14

T4 and T3 to the circulation.

Front 15

80% of secreted thyroid
hormone is .....

Back 15

T4

Front 16

20% of secreted thyroid
hormone is ...

Back 16

T3

Front 17

Regulation of Thyroid Hormone Synthesis-1:

Thyroid releasing hormone
(TRH, hypothalamus)
induces

Back 17

thyroid stimulating hormone(TSH, anterior pituitary) synthesis and secretion.

Front 18

Regulation of Thyroid Hormone Synthesis-1:

TSH acts on thyroid follicular cells to stimulate . .

Back 18

thyroid hormone synthesis and
secretion.

Front 19

Regulation of Thyroid Hormone Synthesis-1:

TSH binding to the
TSH-receptor increases . .

Back 19

cAMP and PKA activity

Front 20

Regulation of Thyroid Hormone Synthesis-2:

TSH stimulates all facets
of thyroid hormone synthesis:

(5 items)

Back 20

- Iodine uptake

-Thyroglobulin synthesis, iodination and coupling to generate iodothyronines

-Storage of iodinated
thyroglobulin in the colloid

-Endocytosis and lysosomal degradation of iodinated thyroglobulin

-Release of T4 and T3 to
the circulation.

- hypertrophy (increase in cell size)

- hyperplasia (increase in cell number)of the thyroid gland.

Front 21

Regulation of Thyroid Hormone Synthesis-3:

Once released, T4 is
converted to

Back 21

T3 by deiodinases in tissues.

Front 22

Regulation of Thyroid Hormone Synthesis-3:

T3 is the , having
effects on various
cells through the
Nuclear T3 RECEPTOR.

Back 22

ACTIVE HORMONE

Front 23

Regulation of Thyroid Hormone Synthesis-4:

Stimulatory and inhibitory
input from

Back 23

- the environment, diet and other endocrine systems.

Front 24

Regulation of Thyroid Hormone Synthesis-4:

Thyroid hormone synthesis
is stimulated by

Back 24

TSH (anterior pituitary thyrotroph)

Front 25

Regulation of Thyroid Hormone Synthesis-4:

TSH secretion is stimulated by

Back 25

TRH (hypothalamic/PVN)

Front 26

Regulation of Thyroid Hormone Synthesis-4:

Somatostatin(hypothalamic/PVN)
inhibits ...

Back 26

TSH secretion,
Leading to suppressed stimulation of T4 synthesis and secretion.

Front 27

Regulation of Thyroid Hormone Synthesis-5:

Feedback Inhibition
by T3

Back 27

- TRH synthesis and secretion

- TSH synthesis (both a and b subunits) and TSH secretion.

Front 28

Regulation of Thyroid Hormone Synthesis-5:

Less TSH results in ...

Back 28

less stimulation of the follicular
cells to synthesize and secrete T4/T3.

Front 29

Transport of Thyroid Hormones

Low affinity: ?

Back 29

Albumin

Front 30

Transport of Thyroid Hormones

High affinity: ? & ?

Back 30

- Thyroxine binding globulin T4: Kd~ 2 x 10-10 M

- Thyroxine binding prealbumin (transthyretin)
T4: Kd~ 2 x 10-10 M

Front 31

Transport of Thyroid Hormones:

Why have transport proteins for hormones?

Back 31

Hydrophobic hormones are insoluble in water, proteins serve as a carrier

b.Hydrophobic hormones are small molecules, transport proteins prevent renal/metabolic clearance

c.Plasma reservoir for the hormone

Front 32

Regulation of Thyroid Hormone Synthesis-5:

Feedback Inhibition
by T3

Back 32

- TRH synthesis and secretion

- TSH synthesis (both a and b subunits) and TSH secretion.

Front 33

Regulation of Thyroid Hormone Synthesis-5:

Less TSH results in ...

Back 33

less stimulation of the follicular
cells to synthesize and secrete T4/T3.

Front 34

Transport of Thyroid Hormones

Low affinity: ?

Back 34

Albumin

Front 35

Transport of Thyroid Hormones

High affinity: ? & ?

Back 35

- Thyroxine binding globulin T4: Kd~ 2 x 10-10 M

- Thyroxine binding prealbumin (transthyretin)
T4: Kd~ 2 x 10-10 M

Front 36

Transport of Thyroid Hormones:

Why have transport proteins for hormones?

Back 36

Hydrophobic hormones are insoluble in water, proteins serve as a carrier

b.Hydrophobic hormones are small molecules, transport proteins prevent renal/metabolic clearance

c.Plasma reservoir for the hormone

Front 37

How Does T3 Regulate Cell Function?

T3, the active hormone is transported
in the blood . . .

Back 37

bound to proteins
e.g., thyroxine binding globulin (TBG).

Front 38

How Does T3 Regulate Cell Function:

T3 Receptors (T3R) are located in . . .

thyroid hormone response elements (TRE)
in promoters of target (regulated) genes.

Back 38

nuclei
bound to target genes with its
heterodimer partner,
Retinoid X receptor (RXR)

Front 39

How Does T3 Regulate Cell Function:

The T3R/RXR heterodimer is bound to . . .

Back 39

thyroid hormone response elements (TRE) in promoters of target (regulated) genes.

Front 40

Mechanism of Thyroid Hormone Action:

T3 must dissociate from its binding proteins (e.g. TBG) to . . .

Back 40

enter cells.

Front 41

Mechanism of Thyroid Hormone Action:

After T3 dissociates from its binding proteins, T3 moves to the ..........

Back 41

nucleus and binds T3 receptors (T3R).

Front 42

Mechanism of Thyroid Hormone Action:

T3 binding to receptors initiates

Back 42

a sequence of events leading to recruitment of RNA polymerase II to the promoter of target (regulated) genes

Front 43

Mechanism of Thyroid Hormone Action:

T3 will induce _________ and inhibit __________ ____________

Back 43

transcription of some genes
and
transcription of other genes.

Front 44

Mechanism of Thyroid Hormone Action:

T3 induces changes in .......

Back 44

the abundance of specific proteins leading to changes in cell function.

Front 45

Physiological Effects of T3 increases . . .

Back 45

- Increases basal metabolic rate (BMR) and oxygen consumption

Front 46

What is BMR?

Back 46

BMR: sum of all body reactions
without mechanical work

Adult BMR = 25 kcal/kg body weight/day

Front 47

Specific examples of the Physiological Effects of T3?

Back 47

- Na-K Pump (+)

- Myosin heavy chain (+)

- b-Adrenergic Receptors (+)

- Enzymes involved in (+):
Fatty acid and
glucose metabolism

- TSH a & b subunits (-)
TRH (-)

Front 48

Effects of Insufficient T3 Production on the Central Nervous System (CNS): Newborns

Back 48

Newborn (Juvenile): Cretinism


-Developmental problems with CNS and somatic growth


-Impaired cognitive function

- Problems with myelinization (myelin basic protein abundance), dendritic outgrowth and arborization

Front 49

Effects of Insufficient T3 Production on the Central Nervous System (CNS): Adults

Back 49

Diminished cognitive function.

Reversible with restoration of T4.

Front 50

Unless T4/T3 is replaced early, the effects on CNS development are ....

Back 50

irreversible.

Front 51

What type of people have their blood levels of T4/T3 tested.

Back 51

All newborns have their blood levels of T4/T3 tested.

Front 52

Endemic Goiter is and does:

Back 52

- Insufficient intake of dietary iodine

[we get iodine in table salt].

- Insufficient dietary iodine impairs T4/T3 synthesis

- Low blood T3 leads to elevated TSH secretion

- Elevated TSH induces hypertrophy & hyperplasia of the gland

- (Goiter) without productive T4/T3 synthesis.

Front 53

3 Thyroidal Diseases

Back 53

- Endemic Goiter

- Graves Disease

- Hashimoto's disease

Front 54

Hashimoto's Disease is

Back 54

- an autoimmune disease.

- Antibodies destroy the thyroid follicular cells leading to a decline in T4/T3 production and Hypothyroidism.

- Hypothyroidism is corrected by giving the patient a synthetic version of T4 (Synthyroid)

Front 55

What is Grave's Disease?

Back 55

- An autoimmune disease.

- Antibodies mimic the action of TSH:
- Induces hypertrophy & hyperplasia of the gland & Enhances T4/T3 production


- Result: Hyperthyroidism

- Anti-thyroidal antibodies are not subject to feedback inhibition

- Therefore, the antibodies have sustained activation of thyroid hormone synthesis without feedback control.


Remedy:

Front 56

Remedy to Grave's disease

Back 56

- Inhibit thyroid hormone synthesis with propyl thiouracil

- Removal of the thyroid gland with surgery or radiation.