Print Email Facebook Twitter Increased glucuronidation of thyroid hormone in hexachlorobenzene-treated rats Title Increased glucuronidation of thyroid hormone in hexachlorobenzene-treated rats Author van Raaij, J.A.G.M. Kaptein, E. Visser, T.J. van den Berg, K.J. Medisch Biologisch Laboratorium TNO Publication year 1993 Abstract Metabolism of thyroid hormones was investigated in WAG/MBL rats that had been exposed to hexachlorobenzene (HCB). Serum thyroxine (T4) levels were lowered by 35.5%, whereas triiodothyronine (T3) levels were not changed. Bile flow, as well as T4 excretion in bile were increased by HCB treatment. Analysis of bile by HPLC revealed a more than 3-fold increase in T4 glucuronide (T4G) and a concomitant reduction of non-conjugated T4. T4 UDP-glucuronyltransferase activity (T4 UDPGT) activity in hepatic microsomes was increased more than 4.5-fold in animals exposed to HCB. p-Nitrophenol (PNP) UDPGT showed a comparable increase by HCB. Both T3 and androsterone UDPGT activities were low in WAG/MBL rats compared with normal Wistar rats. T3 UDPGT activity was increased 2.5-fold by HCB, but androsterone UDPGT activity was unchanged. These results suggest that T4 is a substrate for HCB-inducible PNP UDPGT and T3 for androsterone UDPGT. In the absence of the latter, T3 is also glucuronidated to some extent by PNP UDPGT. Type 1 iodothyronine deiodinase activity was decreased by HCB treatment. It is concluded that decreased T4 levels in serum of animals after exposure to HCB may be due to a combined effect of displacement of T4 from carriers, an increased glucuronidation of T4 and enhanced bile flow. Subject 4 NitrophenolAndrosteroneGlucuronosyltransferaseHexachlorobenzeneLiothyronineRadioisotopeThyroxineAnimal experimentAnimal tissueBile flowBiliary excretionControlled studyDeiodinationEnzyme activityGlucuronidationHigh performance liquid chromatographyHormone blood levelIntraperitoneal drug administrationLiver microsomeMaleNonhumanPriority journalRatThyroid hormone metabolismAndrosteroneAnimalBileGlucuronatesGlucuronosyltransferaseHexachlorobenzeneIodide PeroxidaseMaleMicrosomes, LiverNitrophenolsRatsSupport, Non-U.S. Gov'tThyroid HormonesThyroxineTriiodothyronine To reference this document use: http://resolver.tudelft.nl/uuid:fa1c190c-993d-41bc-9ffa-fd5d21c4ac7a DOI https://doi.org/10.1016/0006-2952(93)90136-k TNO identifier 232235 ISSN 0006-2952 Source Biochemical Pharmacology, 45 (3), 627-631 Bibliographical note Correspondence Address: Van Raaij, J.A.G.M.; TNO Medical Biological Laboratory, PO Box 45, 2280 AA Rijswijk, Netherlands Chemicals/CAS: 4-nitrophenol, 100-02-7; Androsterone, 53-41-8; Glucuronates; Glucuronosyltransferase, EC 126.96.36.199; Hexachlorobenzene, 118-74-1; Iodide Peroxidase, EC 188.8.131.52; Nitrophenols; Thyroid Hormones; Thyroxine, 7488-70-2; Triiodothyronine, 6893-02-3 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.