Hepatic glucuronidation and sulfation of thyroid hormones and their role in regulating thyroidal status in rainbow trout, Oncorhynchus mykiss
| dc.contributor.author | Finnson, Kenneth W. | en_US |
| dc.date.accessioned | 2007-05-18T12:11:27Z | |
| dc.date.available | 2007-05-18T12:11:27Z | |
| dc.date.issued | 1998-05-01T00:00:00Z | en_US |
| dc.degree.discipline | Zoology | en_US |
| dc.degree.level | Doctor of Philosophy (Ph.D.) | en_US |
| dc.description.abstract | Hepatic conjugation of thyroid hormones (TH) was studied in rainbow trout, Oncorhynchus mykiss, and its role in regulating thyroidal status assessed. Conjugated TH were identified in vitro following incubation of isolated hepatocytes with either $\sp{125}$I-labeled thyroxine (T$\sb4$) or 3,5,3$\sp\prime$-triiodothyronine (T$\sb3$) or in bile from trout previously inj cted with either ($\sp{125}$I) T$\sb4$ or ($\sp{125}$I) T$\sb3$. Glucuronidation of T$\sb4$ and T$\sb3$, and sulfation of T$\sb4$ was established in vitro and in vivo. Although sulfation of T$\sb3$ was not established in vitro, sulfated T$\sb3$ and 3,3$\sp\prime$-diiodothyronine (T$\sb2$) were detected in bile. These data indicate that the liver is a major site for glucuronidation and sulfation of TH and that these conjugation pays are involved in biliary excretion of TH. Hepatic glucuronidation of T$\sb4$ and T$\sb3$ was catalyzed by glucuronosyltransferases (GTs) located mainly in the microsomal fraction, using uridine-diphosphoglucuronic acid as cofactor. Hepatic sulfation of TH (T$\sb4$, T$\sb3$ and rT$\sb3$) was catalyzed by sulfotransferases (STs) located mainly in the cytosolic fraction, using 3$\sp\prime$-phosphoadenosine 5$\sp\prime$-phosphosulfate as a sulfate donor. Hepatic deiodination and desulfation of sulfated TH was studied in trout and rat. Unlike the rat, trout hepatic deiodination of sulfated $\sp{125}$I-labeled T$\sb4$, T$\sb3$, or rT$\sb3$ (1 or 1000 nM) was negligible. The role of hepatic glucuronidation and sulfation of TH in regulating thyroidal status in trout was assessed in response to T$\sb3$-treatment and food ration. T$\sb3$-treatment elevated plasma T$\sb3$ levels (2-fold), decreased hepatic T$\sb4$ORD activity, and induced inner-ring deiodination (IRD) of both T$\sb4$ and T$\sb3$ (P $<$ 0.05). The effect of T$\sb3$-treatment on either rT$\sb3$ORD activity, glucuronidation or sulfation of TH was negligible (P $>$ 0.05). In conclusion, glucuronidation and sulfation are important pathways for hepatic metabolism of TH in trout. Both hepatic pathways are involved in biliary excretion of TH, although sulfation may also play a role in cellular storage of TH. In contrast to mammalian systems, sulfation of TH blocks subsequent deiodination and therefore is not a mechanism for salvaging iodine. Although T$\sb3$-treatment and food ration influence thyroidal status by altering hepatic deiodination, food ration can also influence thyroidal status by influencing glucuronidation and sulfation pathways. (Abstract shortened by UMI.) | en_US |
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| dc.format.extent | 184 bytes | |
| dc.format.mimetype | application/pdf | |
| dc.format.mimetype | text/plain | |
| dc.identifier.uri | http://hdl.handle.net/1993/1534 | |
| dc.language.iso | eng | en_US |
| dc.rights | open access | en_US |
| dc.title | Hepatic glucuronidation and sulfation of thyroid hormones and their role in regulating thyroidal status in rainbow trout, Oncorhynchus mykiss | en_US |
| dc.type | doctoral thesis | en_US |