Study your flashcards anywhere!

Download the official Cram app for free >

  • Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off
Reading...
Front

How to study your flashcards.

Right/Left arrow keys: Navigate between flashcards.right arrow keyleft arrow key

Up/Down arrow keys: Flip the card between the front and back.down keyup key

H key: Show hint (3rd side).h key

A key: Read text to speech.a key

image

Play button

image

Play button

image

Progress

1/56

Click to flip

56 Cards in this Set

  • Front
  • Back
Thyroid hormone is a crucial determinant of in ______ ________ _________the body.
growth and development, affecting nearly every tissue
Thyroid hormone is a regulator of ?
overall cellular energy expenditure and substrate utilization.
Thyroid hormone serves to optimize the ?
sensitivity of particular tissues to various other hormones and other factors.
The lack or excess of thyroid hormone can have ?
dramatic effects on the brain, bones, the cardiovascular system and whole body metabolism
Follicular cells make
a precursor protein
of thyroid hormone,
called ??
thyroglobulin.
The iodinated form of
thyroglobulin
is stored in ?
the colloid
The thyroid hormones
are excised from __________
and
are release
- thyroglobulin

- to the circulation.
The Follicular Cell And Its
Role In T4 And T3 synthesis

Iodide (dietary) is activity transported, .....
(with Na+)
into the cell; Requires ATP.
The Follicular Cell And Its
Role In T4 And T3 synthesis

Thyroglobulin (MW~660 kd) is synthesized .....
in the follicular cell.

Thyroglobulin is composed of many tyrosines
The Follicular Cell And Its
Role In T4 And T3 synthesis

At the apical surface of the follicular cells, iodine
is oxidized and attached to thyroglobulin
by a thyroid peroxidase, generating iodotyrosine.
The Follicular Cell And Its
Role In T4 And T3 synthesis:

The iodotyrosines are coupled
to form
iodothyronines.
The Follicular Cell And Its
Role In T4 And T3 synthesis:

Thyroglobulin, with iodothyronines,is stored
in the colloid.

This is a huge reservoir of hormone precursor.
The Follicular Cell And Its
Role In T4 And T3 synthesis:

To get thyroid hormones
into the circulation,
thyroglobulin re-enters the cells by .....
endocytosis.
The Follicular Cell And Its
Role In T4 And T3 synthesis:

Thyroglobulin is degraded by
lysosomal enzymes to release
T4 and T3 to the circulation.
80% of secreted thyroid
hormone is .....
T4
20% of secreted thyroid
hormone is ...
T3
Regulation of Thyroid Hormone Synthesis-1:

Thyroid releasing hormone
(TRH, hypothalamus)
induces
thyroid stimulating hormone(TSH, anterior pituitary) synthesis and secretion.
Regulation of Thyroid Hormone Synthesis-1:

TSH acts on thyroid follicular cells to stimulate . .
thyroid hormone synthesis and
secretion.
Regulation of Thyroid Hormone Synthesis-1:

TSH binding to the
TSH-receptor increases . .
cAMP and PKA activity
Regulation of Thyroid Hormone Synthesis-2:

TSH stimulates all facets
of thyroid hormone synthesis:

(5 items)
- 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.
Regulation of Thyroid Hormone Synthesis-3:

Once released, T4 is
converted to
T3 by deiodinases in tissues.
Regulation of Thyroid Hormone Synthesis-3:

T3 is the , having
effects on various
cells through the
Nuclear T3 RECEPTOR.
ACTIVE HORMONE
Regulation of Thyroid Hormone Synthesis-4:

Stimulatory and inhibitory
input from
- the environment, diet and other endocrine systems.
Regulation of Thyroid Hormone Synthesis-4:

Thyroid hormone synthesis
is stimulated by
TSH (anterior pituitary thyrotroph)
Regulation of Thyroid Hormone Synthesis-4:

TSH secretion is stimulated by
TRH (hypothalamic/PVN)
Regulation of Thyroid Hormone Synthesis-4:

Somatostatin(hypothalamic/PVN)
inhibits ...
TSH secretion,
Leading to suppressed stimulation of T4 synthesis and secretion.
Regulation of Thyroid Hormone Synthesis-5:

Feedback Inhibition
by T3
- TRH synthesis and secretion

- TSH synthesis (both a and b subunits) and TSH secretion.
Regulation of Thyroid Hormone Synthesis-5:

Less TSH results in ...
less stimulation of the follicular
cells to synthesize and secrete T4/T3.
Transport of Thyroid Hormones

Low affinity: ?
Albumin
Transport of Thyroid Hormones

High affinity: ? & ?
- Thyroxine binding globulin T4: Kd~ 2 x 10-10 M

- Thyroxine binding prealbumin (transthyretin)
T4: Kd~ 2 x 10-10 M
Transport of Thyroid Hormones:

Why have transport proteins for hormones?
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
Regulation of Thyroid Hormone Synthesis-5:

Feedback Inhibition
by T3
- TRH synthesis and secretion

- TSH synthesis (both a and b subunits) and TSH secretion.
Regulation of Thyroid Hormone Synthesis-5:

Less TSH results in ...
less stimulation of the follicular
cells to synthesize and secrete T4/T3.
Transport of Thyroid Hormones

Low affinity: ?
Albumin
Transport of Thyroid Hormones

High affinity: ? & ?
- Thyroxine binding globulin T4: Kd~ 2 x 10-10 M

- Thyroxine binding prealbumin (transthyretin)
T4: Kd~ 2 x 10-10 M
Transport of Thyroid Hormones:

Why have transport proteins for hormones?
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
How Does T3 Regulate Cell Function?

T3, the active hormone is transported
in the blood . . .
bound to proteins
e.g., thyroxine binding globulin (TBG).
How Does T3 Regulate Cell Function:

T3 Receptors (T3R) are located in . . .

thyroid hormone response elements (TRE)
in promoters of target (regulated) genes.
nuclei
bound to target genes with its
heterodimer partner,
Retinoid X receptor (RXR)
How Does T3 Regulate Cell Function:

The T3R/RXR heterodimer is bound to . . .
thyroid hormone response elements (TRE) in promoters of target (regulated) genes.
Mechanism of Thyroid Hormone Action:

T3 must dissociate from its binding proteins (e.g. TBG) to . . .
enter cells.
Mechanism of Thyroid Hormone Action:

After T3 dissociates from its binding proteins, T3 moves to the ..........
nucleus and binds T3 receptors (T3R).
Mechanism of Thyroid Hormone Action:

T3 binding to receptors initiates
a sequence of events leading to recruitment of RNA polymerase II to the promoter of target (regulated) genes
Mechanism of Thyroid Hormone Action:

T3 will induce _________ and inhibit __________ ____________
transcription of some genes
and
transcription of other genes.
Mechanism of Thyroid Hormone Action:

T3 induces changes in .......
the abundance of specific proteins leading to changes in cell function.
Physiological Effects of T3 increases . . .
- Increases basal metabolic rate (BMR) and oxygen consumption
What is BMR?
BMR: sum of all body reactions
without mechanical work

Adult BMR = 25 kcal/kg body weight/day
Specific examples of the Physiological Effects of T3?
- Na-K Pump (+)

- Myosin heavy chain (+)

- b-Adrenergic Receptors (+)

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

- TSH a & b subunits (-)
TRH (-)
Effects of Insufficient T3 Production on the Central Nervous System (CNS): Newborns
Newborn (Juvenile): Cretinism


-Developmental problems with CNS and somatic growth


-Impaired cognitive function

- Problems with myelinization (myelin basic protein abundance), dendritic outgrowth and arborization
Effects of Insufficient T3 Production on the Central Nervous System (CNS): Adults
Diminished cognitive function.

Reversible with restoration of T4.
Unless T4/T3 is replaced early, the effects on CNS development are ....
irreversible.
What type of people have their blood levels of T4/T3 tested.
All newborns have their blood levels of T4/T3 tested.
Endemic Goiter is and does:
- 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.
3 Thyroidal Diseases
- Endemic Goiter

- Graves Disease

- Hashimoto's disease
Hashimoto's Disease is
- 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)
What is Grave's Disease?
- 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:
Remedy to Grave's disease
- Inhibit thyroid hormone synthesis with propyl thiouracil

- Removal of the thyroid gland with surgery or radiation.