Thyroid hormone glucuronides

While this pattern of biochemistry does not exclude transient relapse of Graves hyperthyroidism (despite the finding of negative TSH receptor antibodies), or a transient thyroiditis, the authors speculated that indinavir (prescribed in this patient together with stavudine and lamivudine) had inhibited the glucuronidation of thyroxine and hence caused a rise in serum thyroid hormone concentrations. 

TCDD on blood thyroid hormone concentrations, hepatic UDPGT activity, and the consequent increase of serum TSH. This was consistent with the observation that induction of UDPGT results in increased glucuronidation and biliary excretion of T4. The results of Kohn et al. (1996) provided further support to the hypothesis that induction of UDPGT is an early event in the generation of thyroid tumors by 2,3,7,8-TCDD in the rat. 

Henry EC, Gasiewicz TA. 1987. Changes in thyroid hormones and thyroxine glucuronidation in hamsters compared with rats following treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol Appl Pharmacol 89 165-174. 

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... 

Glucuronidation is an important step in the elimination of many important endogenous substances from the body, including bilirubin, bile acids, steroid hormones, thyroid hormones, retinoic acids, and biogenic amines such as serotonin. Many of these compounds are also substrates for sulfonyltransferases (SULTs) (2). 

Visser TJ, Kaptein E, van Toor H, et al. Glucuronidation of thyroid hormone in rat liver effects of in vivo treatment with microsomal enzyme inducers and in vitro assay conditions. Endocrinology 1993 133 2177-2186. 

UGT activity is modulated by various hormones. Excess thyroid hormone and ethinyl oestradiol (but not other oral contraceptives) inhibit bilirubin glucuronidation. In contrast, the combination of progestational and oestrogenic steroids results in increased enzyme activity. Bihrubin glucuronidation can also be inhibited by certain antibiotics (e.g. novobiocin or gentamicin, at serum concentrations exceeding therapeutic levels) and by chronic hepatitis, advanced cirrhosis and Wilson s disease. 

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. 

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