Induction of Cytosolic Triiodo-L-Thyronine (T3) Binding Protein (CTBP) by T3 in Primary Cultured Rat Hepatocytes.

Nishii, Yoshinori; Hashizume, Kiyoshi; Ichikawa, Kazuo; Takeda, Teiji; Kobayashi, Mutsuhiro; Nagasawa, Takeshi; Katai, Miyuki; Kobayashi, Hiroaki; Sakurai, Akihiro

doi:10.1507/endocrj.40.399

Cited by 7 publications

(4 citation statements)

References 16 publications

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“…The absence of effects of T 3 treatment on GST isoenzyme activities (Table 1) or subunits (Table 2) in hepatocytes grown in pyruvate‐supplemented monocultures confirms previous observations that responsiveness to T 3 is maintained in co‐cultures [13,32] but not in monocultures [33,34]. This demonstrates the importance of using the correct culture conditions for studies of in vivo phenomena during in vitro conditions.…”

Section: Resultssupporting

confidence: 85%

Triiodothyronine downregulates the periportal expression of α class glutathione S‐transferase in rat liver

et al. 2001

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Most drug-metabolizing phase I and phase II enzymes, including the glutathione S-transferases (GST), exhibit a zonated expression in the liver, with lower expression in the upstream, periportal region. To elucidate the involvement of pituitary-dependent hormones in this zonation, the effect of hypophysectomy and 3,3P P,5-triiodo-L-thyronine (T 3 ) on the distribution of GST was studied in rats. Hypophysectomy increased total GST activity both in the periportal and perivenous liver region. Subsequent T 3 treatment counteracted this effect in the perivenous zone. However, analysis for either W W class M1/M2-specific (1,2-dichloro-4-nitrobenzene) or K K class A1/A2-specific (7-chloro-4-nitrobenzo-2-oxa-1,3-diazole) GST activity revealed that T 3 treatment did not significantly affect the perivenous activity of these GST classes. In contrast, T 3 was found to significantly counteract the increase of K K class GST activity caused by hypophysectomy in the periportal zone. To establish whether this effect was T 3 -specific, hepatocytes were isolated from either the periportal and perivenous zone by digitonin/collagenase perfusion and cultured either as pyruvatesupplemented monolayer or as co-culture with rat liver epithelial cells. Only in the latter it was found that T 3 suppressed the A1/ A2-specific GST activity and K K class proteins predominantly in periportal cells. The data demonstrate that T 3 is an important factor responsible for the low expression of K K GST in the periportal region. T 3 may be involved in the periportal downregulation of other phase I and II enzymes as well. ß

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Section: Resultssupporting

confidence: 85%

Triiodothyronine downregulates the periportal expression of α class glutathione S‐transferase in rat liver

et al. 2001

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“…We showed previously that rat hepatic cytosol contains thyroid hormone binding protein (cTBP) (Hashizume et al 1991, Nishii et al 1993, Takeda et al 1994, the thyroid hormone binding of which is markedly stimulated by NADPH or NADP and DTT. Subsequent studies revealed that NADPH-activated cTBP inhibits but NADP-DTT-activated cTBP promotes thyroid hormone uptake to nuclei.…”

Section: Discussionmentioning

confidence: 96%

Mechanism of liver-selective thyromimetic activity of SK&F L-94901: evidence for the presence of a cell-type-specific nuclear iodothyronine transport process

Ichikawa¹,

Miyamoto²,

Kakizawa³

et al. 2000

Journal of Endocrinology

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The thyromimetic compound SK&F L-94901 shows more potent thyromimetic activity in the liver than in the pituitary gland or heart when administered to rats. The mechanisms of liver-selectivity of SK&F L-94901 were examined using cultured rat hepatoma cells (dRLH-84) and rat pituitary tumor cells (GH3), both of which showed saturable cellular uptake of tri-iodothyronine (T 3 ). When isolated nuclei with partial disruption of the outer nuclear membrane were used, SK&F L-94901 competed for [ 125 I]T 3 binding to nuclear receptors almost equally in dRLH-84 and GH3 cells. SK&F L-94901 also did not discriminate thyroid hormone receptors (TR) 1 and 1 in terms of binding affinity and activation of the thyroid hormone responsive element. In intact cells, however, SK&F L-94901 was a more potent inhibitor of nuclear [ 125 I]T 3 binding in dRLH-84 cells than in GH3 cells at an early phase of the nuclear uptake process and after binding equilibrium. These data suggest that SK&F L-94901 is more effectively transported to nuclear TRs in hepatic cells than in pituitary cells and therefore shows liverselective thyromimetic activity. In conclusion, SK&F L-94901 discriminates hepatic cells and pituitary cells at the nuclear transport process. The cellular transporters responsible for this discrimination were not evident.

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“…Moreover, a type 3 deiodinase (D3) can inactivate T 3 . Finally, there are cellular binding proteins that may play a role in maintaining intracellular TH levels, or delivering the hormone to the nucleus 23,24 . However, in the brain, this may be cell‐type specific ( 2).…”

Section: Thyroid Hormone Insufficiency—to What Extent Can Compensatormentioning

confidence: 99%

Collision of Basic and Applied Approaches to Risk Assessment of Thyroid Toxicants

THOMAS ZOELLER

2006

Annals of the New York Academy of Sciences

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Thyroid hormone (TH) is essential for normal brain development; therefore, any environmental chemical that interferes sufficiently with thyroid function, TH metabolism, or TH action may exert adverse effects on brain development. Important known differences in aspects of thyroid endocrinology between the fetus, infant, and adult allow us to identify age-dependent vulnerabilities to thyroid toxicants with some confidence. These differences include the size of the hormone pool stored in the thyroid gland at different ages as well as the age-dependent sensitivity to mild TH insufficiency. Several recent studies that describe risk assessments of the environmental contaminant, ammonium perchlorate, provide good examples of conclusions based on the selective consideration of these known aspects of the thyroid system. Specifically, authors who consider age-dependent differences in thyroid endocrinology suggest that safe levels of perchlorate should be set at relatively low levels (low parts per billion). In contrast, authors who do not consider these known age-dependent differences in thyroid endocrinology recommend safe levels of perchlorate at high (hundreds) parts per billion to parts per million. Emerging evidence indicates that a variety of high production volume chemicals can directly interact with the TH receptor. As testing paradigms are designed by regulatory agencies, these age-dependent differences in thyroid endocrinology must be considered.

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Induction of Cytosolic Triiodo-L-Thyronine (T3) Binding Protein (CTBP) by T3 in Primary Cultured Rat Hepatocytes.

Cited by 7 publications

References 16 publications

Triiodothyronine downregulates the periportal expression of α class glutathione S‐transferase in rat liver

Triiodothyronine downregulates the periportal expression of α class glutathione S‐transferase in rat liver

Mechanism of liver-selective thyromimetic activity of SK&F L-94901: evidence for the presence of a cell-type-specific nuclear iodothyronine transport process

Collision of Basic and Applied Approaches to Risk Assessment of Thyroid Toxicants

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