Fate of T4 and T3 hormone

TRANSPORT OF T4 AND T3 IN CIRCULATION

 In circulation most of T3 and T4 are carried by plasma carrier proteins. They are,

1.Thyroxine binding globulin (TBG) – bind 70% of circulating thyroid hormones. It binds 80% T3 and 68% T4.
2.Thyroxine binding prealbumin or transthyretin (TBPA) – binds 20% of circulating thyroid hormones. It binds 9% T3 and 11% T4.
3.Albumin – binds 10% of circulating hormones. It binds 20% T3 and 11% T4.

Thus about 99.97% of T4 and 99.80% of T3 is protein bound. Low-density lipoprotein (LDL) specifically binds and transports <1% of total circulating T4-LDL facilitates entry of T4 into cells by forming a T4-LDL complex that is recognized by the LDL receptor

T4 is more tightly bound than T3 to all these proteins. Approximately 0.2% of T3 and 0.03% of T4 are in free form and are active. So although total T4 is 40 times more than T3 but in free form T4 is only 3 times that of fT3. The half life of T3 is 1-2 days and that of T4 is 5-7 days. In circulation normal T4:T3 ratio is 7:1. This protein bound T4 is the reservoir of T4 and accounts for constant supply of free T4 as well as free T3.

ENTRY OF THYROID HORMONES INTO TISSUE
Specific transporters are involved in transport of thyroid hormones into cells either in peripheral tissue or to brain and neurons.

PERIPHERAL FATE OF THYROID HORMONES
Tg is a preprohormone, T4 is prohormone while T3 performs all the biological actions.  In periphery 45% of T4 is deiodinated to T3 and 45% to rT3 by deiodinases (D1, 2, 3). All these deiodinase are selenoenzymes and requires adequate dietary intake of selenium for their expression. So, normal T4, production of about 100 nmol daily, approximately 40 nmol of T3 and 45 nmol of rT3 are produced by peripheral deiodination. In euthyroid state at least 85% of T3 production and all of rT3 are produced by peripheral deiodination of T4. Peripheral 5’ deiodination of T4 to T3 and 5-deiodination to rT3 is catalyzed by D1 and D2.

D1 carries out either 5’-deiodination giving T3 or 5-deiodination giving inactive rT3 and this enzyme is most abundant found mostly in liver and kidney and is responsible for largest contribution to circulating pool of T3, especially in hypothyroid condition. During hyperthyroidism when T4 is high, T3 production is primarily derived from D1. D2 provides important source of T3 in pituitary, brain and brown adipose tissue as well as in other tissues. This maintains the constant level of T3 in CNS. D3 converts T4 to rT3 and is thought to be important extrathyroidal control mechanism or regulate T3 action. Propylthiouracil and propranolol inhibits the conversion of T4 to T3.

CATABOLISM OF THYROID HORMONES
Sulphation, glucuronidation, deamination, oxidative decarboxylation, ether cleavage and deiodination are the main routes of inactivation and degradation which are excreted via bile or urine.