Thyroid hormones: transport, metabolism and actions

reverse T3 (rT3)

• inactive

• less than 1% secreted

• MIT then DIT

• produced by DIO3

• prevents thyroid hormone access to specific tissues 

what is the least abundant binding protein

thyroxine binding globulin

• but has the highest affinity 

what stimulates and inhibits thyroxine binding globulin

• increased by T4, oestrogens and androgens

• doubles in conc during pregnancy

• lowered by corticosteroids, illness, stress, cirrhosis and nephrotic disorders 

transthyretin

• binds 20% of plasma T4

• important for delivery to CNS

• low affinity but high capacity 

how much does albumin bind to T4

• 5-10%

• very low affinity but highest capacity

which binding proteins bind to T3 vs/and T4

• TBG binds T4 and T3

• transthyretin binds T4 only

• albumin binds T3 and T4

how does free T3 and T4 enter cells

• via transporters

• MCT8, MCT10, OATP1c1

what does iodothyronine deiodinases contain

• seleno cysteine

what within iodothyronine deiodinases will accept the iodine

• selenium

which DIOs are involved in T4 → T3

• DIO1 and DIO2

which DIOs involved in T4 → rT3

DIO! and DIO3

DIO1

• predominates in liver kidney and muscle

• also found in thyroid

• produces most of circulating T3

DIO2

• predominates in CNS and pituitary thyrotropes

• more selective

• controls intracellular T3 conc

• important for feedback regulation

DIO3

• produces inactive rT3

• prevents thyroid hormone access to specific tissues

what does the thyroid hormone receptor form a heterodimer with

• retinoid X receptor

which part of thyroid hormone receptor acts as transcription factor

• heterodimer 

• binds to thyroid response element

• inc affinity for T3 and T4

• inc gene transcription or inhibit gene transcription 

how do thyroid hormones inc transcription

• T3 binds to thyroid receptor

• increases transcription of growth hormone

how does thyroid hormone inhibit transcription

• T3 binds to thyroid receptor

• decreasing prolactin

• decreasing of alpha and beta subunits of TSH

how does thyroid hormone control basal metabolic rate

• inc basal metabolic rate

• inc transcription for tissue growth factor a

• inc sodium and potassium atpase

• inc respiratory enzymes

• inc oxygen consumption → inc metabolic rate

effect of absence of thyroid hormone in children

• arrest of bone elongation

• delayed bone maturation

• reduced growth hormone selection

effect of loss of T4 supply to foetus

• leads to intellectual disability

• dwarfism

• due to iodine deficiency during pregnancy

• leads to endemic congenital iodine deficiency syndrome 

effects of T3 on cardiovascular system

• inc cardiac contraction and output

• inc heart rate

• inc oxygen supply to tissues

• co2 removal

how does T3 directly affect cardiovascular system

• inc myocardial ca2+ uptake,

• inc expression of alpha myosin heavy chain,

• inc expression of RYR in SR

how does T3 indirectly affect cardiovascular system

inc metabolism, vasodilation, inc sensitivity to catecholamines

musculoskeletal effects of T3

• T3 inc formation and reorption of bone

• T3 inc linear bone growth after birth

• T3 increases the rate of muscle relaxation

• normal skeletal muscle function requires T3