Down-Regulation of Type II L-Thyroxine, 5′-Monodeiodinase in Cultured GC Cells

Different Pathways of Regulation by L-Triiodothyronine and 3,3′,5′-Triiodo-L-Thyronine

Yitzchak Halperin, Lawrence E. Shapiro, Martin I. Surks

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The current consensus is that iodothyronines down-regulate type II T4 monodeiodinase (5′-DII) by an extranuclear acceleration of enzyme inactivation. We have investigated 5′-DII regulation in cultured GC cells, in which thyroid hormone responses are mediated by nuclear thyroid receptor (TR). GC cells actively converted T4 to T3, independent of propylthiouracil and with a Km of 1.4 nM, which are characteristics of 5′-DII. When GC cells were incubated with 10 nM T3, the Km, was not affected. However, the maximum velocity was significantly down-regulated by 10 nM T3, from 0.15 to 0.018 pmol/mg protein · min. Dose-response studies showed that a 50% reduction in enzyme activity was achieved with either 0.25 nM T3 or 12 nM rT3. Time-course studies showed that a 50% reduction in enzyme activity occurred after 40 min of incubation with 100 nM rT3 and after 160 min of incubation with 10 nM T3. The down-regulation of 5′-DII by physiological concentrations of T3 has the characteristics of an effect that is mediated by nuclear TR. Our studies, therefore, suggest that down-regulation of 5′-DII by these iodothyronines in GC cells may occur by different mechanisms: enzyme inactivation for rT3, in agreement with the current consensus, and decreased enzyme production for T3, probably mediated by TR.

Original languageEnglish (US)
Pages (from-to)1464-1469
Number of pages6
JournalEndocrinology
Volume135
Issue number4
StatePublished - Oct 1994

Fingerprint

Thyronines
Iodide Peroxidase
Triiodothyronine
Thyroxine
Cultured Cells
Down-Regulation
Enzymes
Thyroid Gland
Cytoplasmic and Nuclear Receptors
Propylthiouracil
Thyroid Hormones
Proteins

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Down-Regulation of Type II L-Thyroxine, 5′-Monodeiodinase in Cultured GC Cells : Different Pathways of Regulation by L-Triiodothyronine and 3,3′,5′-Triiodo-L-Thyronine. / Halperin, Yitzchak; Shapiro, Lawrence E.; Surks, Martin I.

In: Endocrinology, Vol. 135, No. 4, 10.1994, p. 1464-1469.

Research output: Contribution to journalArticle

@article{ca78ff5f7026490daaeb2318b596745d,
title = "Down-Regulation of Type II L-Thyroxine, 5′-Monodeiodinase in Cultured GC Cells: Different Pathways of Regulation by L-Triiodothyronine and 3,3′,5′-Triiodo-L-Thyronine",
abstract = "The current consensus is that iodothyronines down-regulate type II T4 monodeiodinase (5′-DII) by an extranuclear acceleration of enzyme inactivation. We have investigated 5′-DII regulation in cultured GC cells, in which thyroid hormone responses are mediated by nuclear thyroid receptor (TR). GC cells actively converted T4 to T3, independent of propylthiouracil and with a Km of 1.4 nM, which are characteristics of 5′-DII. When GC cells were incubated with 10 nM T3, the Km, was not affected. However, the maximum velocity was significantly down-regulated by 10 nM T3, from 0.15 to 0.018 pmol/mg protein · min. Dose-response studies showed that a 50{\%} reduction in enzyme activity was achieved with either 0.25 nM T3 or 12 nM rT3. Time-course studies showed that a 50{\%} reduction in enzyme activity occurred after 40 min of incubation with 100 nM rT3 and after 160 min of incubation with 10 nM T3. The down-regulation of 5′-DII by physiological concentrations of T3 has the characteristics of an effect that is mediated by nuclear TR. Our studies, therefore, suggest that down-regulation of 5′-DII by these iodothyronines in GC cells may occur by different mechanisms: enzyme inactivation for rT3, in agreement with the current consensus, and decreased enzyme production for T3, probably mediated by TR.",
author = "Yitzchak Halperin and Shapiro, {Lawrence E.} and Surks, {Martin I.}",
year = "1994",
month = "10",
language = "English (US)",
volume = "135",
pages = "1464--1469",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "4",

}

TY - JOUR

T1 - Down-Regulation of Type II L-Thyroxine, 5′-Monodeiodinase in Cultured GC Cells

T2 - Different Pathways of Regulation by L-Triiodothyronine and 3,3′,5′-Triiodo-L-Thyronine

AU - Halperin, Yitzchak

AU - Shapiro, Lawrence E.

AU - Surks, Martin I.

PY - 1994/10

Y1 - 1994/10

N2 - The current consensus is that iodothyronines down-regulate type II T4 monodeiodinase (5′-DII) by an extranuclear acceleration of enzyme inactivation. We have investigated 5′-DII regulation in cultured GC cells, in which thyroid hormone responses are mediated by nuclear thyroid receptor (TR). GC cells actively converted T4 to T3, independent of propylthiouracil and with a Km of 1.4 nM, which are characteristics of 5′-DII. When GC cells were incubated with 10 nM T3, the Km, was not affected. However, the maximum velocity was significantly down-regulated by 10 nM T3, from 0.15 to 0.018 pmol/mg protein · min. Dose-response studies showed that a 50% reduction in enzyme activity was achieved with either 0.25 nM T3 or 12 nM rT3. Time-course studies showed that a 50% reduction in enzyme activity occurred after 40 min of incubation with 100 nM rT3 and after 160 min of incubation with 10 nM T3. The down-regulation of 5′-DII by physiological concentrations of T3 has the characteristics of an effect that is mediated by nuclear TR. Our studies, therefore, suggest that down-regulation of 5′-DII by these iodothyronines in GC cells may occur by different mechanisms: enzyme inactivation for rT3, in agreement with the current consensus, and decreased enzyme production for T3, probably mediated by TR.

AB - The current consensus is that iodothyronines down-regulate type II T4 monodeiodinase (5′-DII) by an extranuclear acceleration of enzyme inactivation. We have investigated 5′-DII regulation in cultured GC cells, in which thyroid hormone responses are mediated by nuclear thyroid receptor (TR). GC cells actively converted T4 to T3, independent of propylthiouracil and with a Km of 1.4 nM, which are characteristics of 5′-DII. When GC cells were incubated with 10 nM T3, the Km, was not affected. However, the maximum velocity was significantly down-regulated by 10 nM T3, from 0.15 to 0.018 pmol/mg protein · min. Dose-response studies showed that a 50% reduction in enzyme activity was achieved with either 0.25 nM T3 or 12 nM rT3. Time-course studies showed that a 50% reduction in enzyme activity occurred after 40 min of incubation with 100 nM rT3 and after 160 min of incubation with 10 nM T3. The down-regulation of 5′-DII by physiological concentrations of T3 has the characteristics of an effect that is mediated by nuclear TR. Our studies, therefore, suggest that down-regulation of 5′-DII by these iodothyronines in GC cells may occur by different mechanisms: enzyme inactivation for rT3, in agreement with the current consensus, and decreased enzyme production for T3, probably mediated by TR.

UR - http://www.scopus.com/inward/record.url?scp=0028049755&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028049755&partnerID=8YFLogxK

M3 - Article

VL - 135

SP - 1464

EP - 1469

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 4

ER -