Thyroid Physiology II

Question 1

Are extremely hydrophobic and hence, readily enter target cells by passive diffusion across outer and nuclear membranes

Answer 1

T3 and T4

Question 2

Once in the nucleus, T3 and T4 specifically bind to their

Answer 2

Cognate receptors

Question 3

The receptors for thyroid hormone (thyroid hormone receptors or TRs) are members of the nuclear hormone receptor superfamily that serve as

Answer 3

Ligand-activated transcription regulatory proteins

Question 4

There are two very similar human TR subtypes, α and β, encoded on two different genes found on chromosomes

Answer 4

17 and 3 respectively

Question 5

Both TRa and TRB bind to DNA as a heterodimer with another nuclear hormone called

Answer 5

RXR

Question 6

Specific DNA sequesnces that serve as binding sites for RXR/TR and are found in the promoter region of target genes

Answer 6

Thyroid Hormone Response Elements (TREs)

Question 7

In the absence of hormone, RXR/TR can still bind to DNA, but the unliganded receptors usually facilitate transcriptional repression (i.e., gene silencing) via the recruitment of

Answer 7

Corepressor proteins

Question 8

TR undergoes a conformational change that allows it to recruit coactivator proteins and enzymes in the presence of

Answer 8

T3

Question 9

This typically results in strong transcriptional activation of the

Answer 9

Target gene

Question 10

Which binds TR with a greater affinity of approximately 100x, T3 or T4?

Answer 10

T3

Question 11

Because thyroid hormone acts at the level of gene expression, man of its effects can be blocked by inhibitors of

Answer 11

Protein synthesis (such as cycloheximide)

Question 12

This also accounts for the 12- to 48-hour delay (or latent

period) before most of thyroid hormones’ physiological effects become

Answer 12

Evident in vivo

Question 13

The best documented physiological effect of thyroid hormone is to increase almost every tissue types (except the brain, spleen, and testes)?

Answer 13

Basal Metabolic Rate (BMR)

Question 14

The hormone induced increase in BMR is associated with a significant increase in

Answer 14

Oxygen consumption and production of heat

Question 15

Stimulates the BMR in part by increasing the
number and size of mitochondria as well as directly upregulating the expression of mitochondrial respiratory enzymes required for increased ATP production

Answer 15

Thyroid Hormone

Question 16

To compensate for the increased demand for oxygen (the result of an elevated BMR), thyroid hormones act directly and indirectly on cardiac muscle, having what effect?

Answer 16

Increase contractility and cardiac output

Question 17

The direct effects of thyroid hormone on cardiac muscle are evident as an upregulation in

Answer 17

Actin, myosin, and Ca2+ and myosin stimulated ATPases

Question 18

Indirect effects include enhancing the speed and force of myocardial contractions by potentiating stimulation by the

Answer 18

SNS

Question 19

Indirectly upregulates the expression of beta adrenergic receptors in cardiac muscle cells

Answer 19

Thyroif hormone

Question 20

Physiologically, increased oxygen consumption (the result of an elevated BMR) must be accompanied by increased

Answer 20

Energy consumption

Question 21

Thyroid hormone increases cellular energy expenditure by activating the expression of the

Answer 21

Na+/K+ ATPase

Question 22

As much as 20-80% of the basal energy used by a resting cell is devoted towards maintaining the gradient produced by the

Answer 22

Na+/K+ ATPase

Question 23

The Na+/K+ ATPase generates large amounts of

Answer 23

ADP and heat

Question 24

Also increase energy expenditure by stimulating futile cycling of protein, carbohydrate and fat metabolism (i.e., simultaneously stimulating both anabolic and catabolic pathways)

Answer 24

Thyroid Hormones

Question 25

In general, leads to an overall increase in protein, | lipid and glycogen turnover with the catabolic pathways ultimately predominating

Answer 25

Hyperthyroidism

Question 26

Thus, hyperthyroid patients tend to

Answer 26

Lose weight

Question 27

Leads to an overall decrease in metabolic turnover

Answer 27

Hypothyroidism

Question 28

Thyroid hormones are important in maintaining a constant body temperature. This is called

Answer 28

Thermoregulation

Question 29

Have an elevated body temperature and a lower tolerance to heat

Answer 29

Hyperthyroid patients

Question 30

Experience a decreased tolerance to cold

Answer 30

Hypothyroid patients

Question 31

T3/T4’s ability to increase oxygen consumption and generate body heat can also be accounted for through a process termed

Answer 31

Facultative thermogenesis

Question 32

In brown adipose tissue (BAT), T3/T4 acts in concert with stimulation from the sympathetic nervous system (SNS) to upregulate the expression of

Answer 32

Uncoupling protein-1 (UCP-1)

Question 33

Acts in the mitochondria to create a ‘leakage’ of protons across the inner mitochondrial membrane essentially short-circuiting the respiratory chain

Answer 33

UCP-1

Question 34

Thus, although oxygen continues to be utilized at a high rate, very little ATP is synthesized. Rather, most of the available energy is simply lost as

Answer 34

Heat

Question 35

Crucial for normal linear growth of adolescents into | adults and attainment of a normal adult stature depends on optimal levels

Answer 35

Thyroid hormone

Question 36

Early in infancy, thyroid hormone is required for the synthesis of

Answer 36

hGH (aka somatotropin)

Question 37

Biochemical studies suggest thyroid hormone can directly stimulate osteoblasts to produce

Answer 37

IGF-1, alkaline phosphatase, and osteocalcin

Question 38

Thyroid hormone is thought to function synergistically with hGH and other insulin-like growth factors (somatomedins) to promote

Answer 38

Linear bone growth

Question 39

Uncorrected hypothyroidism during childhood results in linear growth retardation and malformation of facial bones. This condition is termed as

Answer 39

Juvenile hypothyroidism or cretinism

Question 40

In adults, excess T4/T3 (hyperthyroidism) promotes

Answer 40

Osteoporosis

Question 41

Are essential for the normal development and maturation of the CNS during fetal development and early infancy

Answer 41

Thyroid hormones

Question 42

The most important period for thyroid hormone action on the CNC -the period just before and just after birth during which there is an absolute requirement for thyroid hormone signaling

Answer 42

Perinatal period

Question 43

Promotes the development and maturation of the CNS by regulating myelinogenesis and synapse formation as well as neuronal outgrowth, proliferation, and differentiation

Answer 43

T4/T3

Question 44

During the critical perinatal period, thyroid hormone must be present for the normal development of the

Answer 44

Brain

Question 45

Results in severe, irreversible mental retardation, even if large doses of T4/T3 are given later in life

Answer 45

Neonatal hypothyroidism

Question 46

Neonatal hypothyroidism can be averted by

Answer 46

Immediate post natal administration of T4/T3

Question 47

Produces hyperexciteability, irritability, and restlessness in adults

Answer 47

Hyperthyroidism

Question 48

Display listlessness, lack of energy, slowness of speech, decreased sensory capacity and impaired memory

Answer 48

Hypothyroid adults

Question 49

The most common cause of hyperthyroidism is an autoimmune stimulation of thyroid follicular cell TSH receptors called

Answer 49

Grave's disease

Question 50

Results in hyperplasia of the entire thyroid gland and unsuppressed production of T3/T4

Answer 50

Grave’s Disease

Question 51

The second most common cause of hyperthyroidism is

Answer 51

Benign neoplasms in thyroid

Question 52

The least common causes are excessive pituitary secretion of TSH, ingestion of exogenous T3/T4, and hyper-activating mutations of TR genes

Answer 52

Hyperthyroidism

Question 53

In most cases of hyperthyroidism, there is an excessive thyroid uptake of

Answer 53

Iodine

Question 54

Serum TSH levels are concomitantly low because the hypothalamus and pituitary glands are suppressed by the high levels of

Answer 54

T3/T4

Question 55

Are there cases of hyperthyroidism where both T3/T4 levels and TSH levels are high?

Answer 55

Yes

Question 56

The symptoms of hyperthyroidism in adults are striking and are primarily due to an elevated

Answer 56

Metabolic rate

Question 57

Excitability and nervousness are due to the action of T3/T4 on the

Answer 57

CNS

Question 58

Can cause eye ball protrusion (exopthalmos) due to edematous swelling of the retro orbital tissues and degenerative changes in the extraoccular muscles

Answer 58

Hyperthyroidism

Question 59

Exopthalmos is not due to elevated T3/T4 levels, but rather the result of

Answer 59

Anit-TSH receptor autoimmunity

Question 60

What are three possible treatments of hyperthyroidism?

Answer 60

1. ) Propylthiouracil 2. ) radioactive thyroid ablasion 3. ) Surgical removal of thyroid

Question 61

Inhibits the enzymatic action of TPO

Answer 61

Propylthiouracil

Question 62

The most common cause of hypothyroidism is an autoimmune destruction of the thyroid gland (thyroiditis) in which antibodies either block T3/T4 synthesis or cause atrophy of the gland. An example of this is

Answer 62

Hashimoto's Thyroditis

Question 63

Hypothalamus or pituitary disorders that inhibit TSH | secretion, or iodine deficiency in the diet can both cause

Answer 63

Hypothyroidism

Question 64

Iodine deficiency in the diet is known as

Answer 64

Endemic cretinism

Question 65

In rare cases, mutant TR's can cause

Answer 65

Hypothyroidism

Question 66

Hypothyroidism due to a mutation in a TR is called

Answer 66

Generalized resistance to thyroid hormone

Question 67

IF the hypothyroidism is caused by hypothalamic or pituitary failure than TSH will be

Answer 67

Decreased

Question 68

Otherwise, Hypothyroidism means that TSH is

Answer 68

Elevated

Question 69

Weight gain, decreased heart rate and cardiac output, and decreased heat production (and thus cold intolerance) are common with

Answer 69

Hypothyroidism

Question 70

Movement, speech and thought are all slowed and lethargy, sleepiness, and a lowering of the upper eyelids (ptosis) occur with

Answer 70

Hypothyroidism

Question 71

An accumulation of mucopolysaccharides in various tissues can occur which in turn results in a diffuse accumulation of extracellular fluid termed

Answer 71

Myxedema

Question 72

When the primary disorder of hypothyroidism is at the level of the thyroid gland itself, goiter can occur due to the relentless stimulation of the thyroid gland by high circulating levels of

Answer 72

TSH

Question 73

Treatment for hypothyroidism involves -in most cases is entirely curative

Answer 73

T4 hormone replacement therapy

Question 74

Is generally not used to treat hypothyroidism given its short ½-life in the blood stream

Answer 74

T3