Thyroid Hormone Regulates Type I Deiodinase Messenger RNA in Rat Liver

Liver uptake of thyroxine (T4) is mediated by transporters and is rate limiting for hepatic 3,3′,5-triiodothyronine (T3) production. We investigated whether hepatic mRNA for T4transporters is regulated by thyroid state using Xenopus laevis oocytes as an expression system. Because X. laevis oocytes show high endogenous uptake of T4, T4 sulfamate (T4NS) was used as an alternative ligand for the hepatic T4 transporters. Oocytes were injected with 23 ng liver mRNA from euthyroid, hypothyroid, or hyperthyroid rats, and after 3–4 days uptake was determined by incubation of injected and uninjected oocytes for 1 h at 25°C or for 4 h at 18°C with 10 nM [125I]T4NS. Expression of type I deiodinase (D1), which is regulated by thyroid state, was studied in the oocytes as an internal control. Uptake of T4NS showed similar approximately fourfold increases after injection of liver mRNA from euthyroid, hypothyroid, or hyperthyroid rats. A similar lack of effect of thyroid state was observed using reverse T3 as ligand. In contrast, D1 activity induced by liver mRNA from hyperthyroid and hypothyroid rats in the oocytes was 2.4-fold higher and 2.7-fold lower, respectively, compared with euthyroid rats. Studies have shown that uptake of iodothyronines in rat liver is mediated in part by several organic anion transporters, such as the Na+/taurocholate-cotransporting polypeptide (rNTCP) and the Na-independent organic anion-transporting polypeptide (rOATP1). Therefore, the effects of thyroid state on rNTCP, rOATP1, and D1 mRNA levels in rat liver were also determined. Northern analysis showed no differences in rNTCP or rOATP1 mRNA levels between hyperthyroid and hypothyroid rats, whereas D1 mRNA levels varied widely as expected. These results suggest little effect of thyroid state on the levels of mRNA coding for T4 transporters in rat liver, including rNTCP and rOATP1. However, they do not exclude regulation of hepatic T4 transporters by thyroid hormone at the translational and posttranslational level.

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Tissue distribution and regulation of 5′-deiodinase processes in lactating rats

Journal of Endocrinology ◽

10.1677/joe.0.1420205 ◽

1994 ◽

Vol 142 (2) ◽

pp. 205-215 ◽

Cited By ~ 29

Author(s):

L J W Jack ◽

S Kahl ◽

D L St Germain ◽

A V Capuco

Keyword(s):

Mammary Gland ◽

Rat Liver ◽

Messenger Rna ◽

Northern Blotting ◽

Type I ◽

Mrna Levels ◽

Lactating Mammary Gland ◽

Liver And Kidney ◽

Rat Mammary Gland ◽

Polymerase Chain

Abstract Thyroxine 5′-deiodinase (5′D) catalyses deiodination of the prohormone thyroxine (T4) to the metabolically active hormone 3,5,3′-tri-iodothyronine (T3). Previously, it has been demonstrated that rat mammary gland expresses a 5′D with enzymatic properties equivalent to those of the type I enzyme (5′D-I) found in rat liver and kidney. Using complementary DNA (cDNA) for rat hepatic 5′D-I, we have examined expression of 5′D-I messenger RNA (mRNA) in liver, and mammary gland from virgin and lactating rats, and in seven other tissues from virgin rats. 5′D-I mRNA could not be detected in mammary gland either by Northern blotting or by the more sensitive technique of reverse transcribing mRNA and then amplifying the cDNA by polymerase chain reaction (RTPCR). Analysis of the seven tissues from virgin rats by RT-PCR showed 5′D-I amplicons in liver, kidney and thyroid. No amplicons were detected in adrenal gland, cardiac muscle, skeletal muscle or spleen. In addition, the effect of lactation intensity on circulating thyroid hormones, hepatic and mammary gland 5′D activity, and hepatic 5′D-I mRNA levels was examined. A strong inverse relationship was noted between increased lactation intensity (suckling burden) and circulating T4 and T3, hepatic 5′D-I activity and hepatic 5′D-I mRNA levels. Mammary gland 5′D activity was positively correlated to lactation intensity. The data presented strongly suggest that the 5′D activity expressed in lactating mammary gland is encoded by a mRNA different from the 5′D-I message found in rat liver, kidney and thyroid gland, and may help explain the differential regulation of 5′D-I activity in these organs during lactation. In addition, hepatic 5′D-I activity was found to be correlated with the concentration of 5′D-I mRNA, suggesting that regulation is pretranslational. Results are consistent with a previously suggested involvement of 5′D in establishing metabolic adaptations to support lactation. Journal of Endocrinology (1994) 142, 205–215

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