Sulfation thyroid hormones

The functional form of thyroxine (T3) is generated by the deiodination of T4, and PCBs can influence the tissue levels of this form by disturbing metabolism, as well as by reducing the binding of T4. PCBs have been shown to inhibit the sulfation of thyroid hormones and the deiodination of T4 to T3. They can also induce the glucuronyl transferase that conjugates T4 (Brouwer et al. 1998). 

Current information indicates that OATP-E [30] is ubiquitously expressed in tissues [30, 37]. Some substrates transported by OATP-E include estrone-sulfate [30], prostaglandin E2 [30] and taurocholate [37]. The capacity for T3 and T4 transport and the wide tissue distribution suggests that OATP-E is largely responsible for the peripheral uptake of thyroid hormone [37]. Further studies are required to assess whether OATP-E is an important determinant of drag distribution. 

The OATP-C, also referred to as liver specific transporter 1 (LST-1) or OATP2, was cloned by number of groups (8,24,25) and was shown to be exclusively expressed in the basolateral membrane of the liver (25). As with OATP-A, OATP-C has broad substrate specificity and transports bile acids (13), sulfate and glucuronide conjugates (25), thyroid hormones (13), and peptides (16), and drugs such as pravastatin (24), methotrexate (26), and rifampin (27). Given its liver-specific expression and broad substrate... 

SULT 1B1 functions in the sulfation of diverse endogenous substrates include cholesterol, dehydroepiandrosterone (DHEA), thyroid hormone, and dopamine. The enzyme also contributes to the metabolism of phenolic xenobiotics such as those containing 2-naphthol. It is highly expressed in the liver, colon, small intestine, and blood leukocytes. 

OATP1A2 is capable of transporting diverse compounds, including BSP, bile acids, steroid sulfates, bulky organic cations, fexofenadine, thyroid hormones, and... 

Schuur AG, Cenjin PH, van Toor H, et al. 1998a. Effect of Aroclor 1254 on thyroid hormone sulfation in fetal rats. In Johansson N, Bergman A, Broman D, et al., ed. Organohalogen compounds. Akademitryck, Edsbruk , Vol. 37, 249-252. 

Schuur AG, van Leeuwen-Bol I, Jong WMC, et al. 1998b. In vitro inhibition of thyroid hormone sulfation by polychloribiphenylols Isozyme specificity and inhibition kinetics. Toxicol Sci 45 188-194. 

Some thyroid hormones are conjugated in the liver and excreted in the bile as sulfates or glucuronides, while small amounts of free hormones and the iodoacetic acid form break down products (Hood and Klaassen 2000a, 2000b Klaassen and Hood 2001). The half-lives of T4 and T3 are much shorter in laboratory animals (16 and 6 h in the dog and rat, respectively) than for humans, where the half-life of circulating T4 is approximately 5-7 days and is about 1-2 days for T3. 

A wide range of serum thyroid hormones (T4, FT4, T3, reverse triiodothyronine (rT3), thyroxine sulfate (T4S)), TSH and thyroid binding globulin (TBG) were analyzed in our studies T4, but not FT4 levels were indicative of hypothyroxinemia (Williams et at, 2004 Simpson et at, 2005). In 23—27 week gestation infants, T4 serum levels decrease to a nadir at 7 postnatal days and fail to increase in 28—30 week infants. This is in marked contrast to 31—34 and 37—42 week term infants, who show an increase in serum T4 levels at day 7 (Williams et al., 2004 Simpson et at, 2005). 

Further metabolism of the thyroid hormones takes place in the liver and kidneys by deamination, decarboxylation, sulfatation or conjugation, but especially by deiodination, whereby around 20% of the iodide, which is set free, is reused for the synthesis of thyroxine. The biological half-life of thyroxine is around 190 hours that of 3,3 ,5-triiodothyronine is 19 hours. About 15% of the thyroid hormones are excreted via the faeces, and only minor amounts into the urine. 

Therapeutic measures which have been applied in both diseases, other than dietary prescriptions and symptomatic therapy, are few. The most important therapy is with estrogenic substances, the next that with thyroid hormone and related substances, and the third that with magnesium sulfate given parenterally. The role of hormones in cardiovascular disease has very recently been reviewed by Oliver and Boyd (1958). 

---