Mice with impaired extrathyroidal thyroxine to 3,5,3′- triiodothyronine conversion maintain normal serum 3,5,3′-triiodothyronine concentrations

Marcelo A. Christoffolete, Rafael Arrojo E Drigo, Fernanda Gazoni, Susana M. Tente, Vanessa Goncalves, Beatriz S. Amorim, P. Reed Larsen, Antonio C. Bianco, Ann Marie Zavacki

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

For T3 to mediate its biological effects, the prohormone T 4 must be activated by removal of an outer-ring iodine by the type 1 or 2 deiodinases (D1 and D2) with approximately 60% of the daily T3 production in rodents being produced extrathyroidally through this pathway. To further define the role of these enzymes in thyroid hormone homeostasis, we backcrossed the targeted disruption of the Dio2 gene into C3H/HeJ (C3H) mice with genetically low D1 expression to create the C3H-D2KO mouse. Remarkably, these mice maintain euthyroid serum T3 levels with normal growth and no decrease in expression of hepatic T3-responsive genes. However, serum T4 is increased 1.2-fold relative to the already elevated C3H levels, and serum TSH is increased 1.4-fold. Despite these increases, thyroidal 125I uptake indicates no difference in thyroidal activity between C3H-D2KO and C3H mice. Although C3H-D2KO hepatic and renal D1 activities were well below those observed in wild-type mice (∼0.1-fold for both), they were 8-fold and 2-fold higher, respectively, relative to C3H mice. Thyroidal D1 and cerebral cortical type 3 deiodinase activity were unchanged between C3H-D2KO and C3H mice. In conclusion, C3H-D2KO mice have notably elevated serum T 4 levels, and this, in conjunction with residual D1 activity, is likely an important role in the maintenance of euthyroid serum T3 concentrations.

Original languageEnglish
Pages (from-to)954-960
Number of pages7
JournalEndocrinology
Volume148
Issue number3
DOIs
StatePublished - Mar 1 2007

Fingerprint

Inbred C3H Mouse
Triiodothyronine
Thyroxine
Serum
Iodide Peroxidase
Liver
Thyroid Hormones
Iodine
Genes
Rodentia
Homeostasis
Maintenance
Kidney
Enzymes
Growth

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Christoffolete, M. A., Arrojo E Drigo, R., Gazoni, F., Tente, S. M., Goncalves, V., Amorim, B. S., ... Zavacki, A. M. (2007). Mice with impaired extrathyroidal thyroxine to 3,5,3′- triiodothyronine conversion maintain normal serum 3,5,3′-triiodothyronine concentrations. Endocrinology, 148(3), 954-960. https://doi.org/10.1210/en.2006-1042

Mice with impaired extrathyroidal thyroxine to 3,5,3′- triiodothyronine conversion maintain normal serum 3,5,3′-triiodothyronine concentrations. / Christoffolete, Marcelo A.; Arrojo E Drigo, Rafael; Gazoni, Fernanda; Tente, Susana M.; Goncalves, Vanessa; Amorim, Beatriz S.; Larsen, P. Reed; Bianco, Antonio C.; Zavacki, Ann Marie.

In: Endocrinology, Vol. 148, No. 3, 01.03.2007, p. 954-960.

Research output: Contribution to journalArticle

Christoffolete, MA, Arrojo E Drigo, R, Gazoni, F, Tente, SM, Goncalves, V, Amorim, BS, Larsen, PR, Bianco, AC & Zavacki, AM 2007, 'Mice with impaired extrathyroidal thyroxine to 3,5,3′- triiodothyronine conversion maintain normal serum 3,5,3′-triiodothyronine concentrations', Endocrinology, vol. 148, no. 3, pp. 954-960. https://doi.org/10.1210/en.2006-1042
Christoffolete, Marcelo A. ; Arrojo E Drigo, Rafael ; Gazoni, Fernanda ; Tente, Susana M. ; Goncalves, Vanessa ; Amorim, Beatriz S. ; Larsen, P. Reed ; Bianco, Antonio C. ; Zavacki, Ann Marie. / Mice with impaired extrathyroidal thyroxine to 3,5,3′- triiodothyronine conversion maintain normal serum 3,5,3′-triiodothyronine concentrations. In: Endocrinology. 2007 ; Vol. 148, No. 3. pp. 954-960.
@article{514c3cd775f64ef998b836138883bd05,
title = "Mice with impaired extrathyroidal thyroxine to 3,5,3′- triiodothyronine conversion maintain normal serum 3,5,3′-triiodothyronine concentrations",
abstract = "For T3 to mediate its biological effects, the prohormone T 4 must be activated by removal of an outer-ring iodine by the type 1 or 2 deiodinases (D1 and D2) with approximately 60{\%} of the daily T3 production in rodents being produced extrathyroidally through this pathway. To further define the role of these enzymes in thyroid hormone homeostasis, we backcrossed the targeted disruption of the Dio2 gene into C3H/HeJ (C3H) mice with genetically low D1 expression to create the C3H-D2KO mouse. Remarkably, these mice maintain euthyroid serum T3 levels with normal growth and no decrease in expression of hepatic T3-responsive genes. However, serum T4 is increased 1.2-fold relative to the already elevated C3H levels, and serum TSH is increased 1.4-fold. Despite these increases, thyroidal 125I uptake indicates no difference in thyroidal activity between C3H-D2KO and C3H mice. Although C3H-D2KO hepatic and renal D1 activities were well below those observed in wild-type mice (∼0.1-fold for both), they were 8-fold and 2-fold higher, respectively, relative to C3H mice. Thyroidal D1 and cerebral cortical type 3 deiodinase activity were unchanged between C3H-D2KO and C3H mice. In conclusion, C3H-D2KO mice have notably elevated serum T 4 levels, and this, in conjunction with residual D1 activity, is likely an important role in the maintenance of euthyroid serum T3 concentrations.",
author = "Christoffolete, {Marcelo A.} and {Arrojo E Drigo}, Rafael and Fernanda Gazoni and Tente, {Susana M.} and Vanessa Goncalves and Amorim, {Beatriz S.} and Larsen, {P. Reed} and Bianco, {Antonio C.} and Zavacki, {Ann Marie}",
year = "2007",
month = "3",
day = "1",
doi = "10.1210/en.2006-1042",
language = "English",
volume = "148",
pages = "954--960",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "3",

}

TY - JOUR

T1 - Mice with impaired extrathyroidal thyroxine to 3,5,3′- triiodothyronine conversion maintain normal serum 3,5,3′-triiodothyronine concentrations

AU - Christoffolete, Marcelo A.

AU - Arrojo E Drigo, Rafael

AU - Gazoni, Fernanda

AU - Tente, Susana M.

AU - Goncalves, Vanessa

AU - Amorim, Beatriz S.

AU - Larsen, P. Reed

AU - Bianco, Antonio C.

AU - Zavacki, Ann Marie

PY - 2007/3/1

Y1 - 2007/3/1

N2 - For T3 to mediate its biological effects, the prohormone T 4 must be activated by removal of an outer-ring iodine by the type 1 or 2 deiodinases (D1 and D2) with approximately 60% of the daily T3 production in rodents being produced extrathyroidally through this pathway. To further define the role of these enzymes in thyroid hormone homeostasis, we backcrossed the targeted disruption of the Dio2 gene into C3H/HeJ (C3H) mice with genetically low D1 expression to create the C3H-D2KO mouse. Remarkably, these mice maintain euthyroid serum T3 levels with normal growth and no decrease in expression of hepatic T3-responsive genes. However, serum T4 is increased 1.2-fold relative to the already elevated C3H levels, and serum TSH is increased 1.4-fold. Despite these increases, thyroidal 125I uptake indicates no difference in thyroidal activity between C3H-D2KO and C3H mice. Although C3H-D2KO hepatic and renal D1 activities were well below those observed in wild-type mice (∼0.1-fold for both), they were 8-fold and 2-fold higher, respectively, relative to C3H mice. Thyroidal D1 and cerebral cortical type 3 deiodinase activity were unchanged between C3H-D2KO and C3H mice. In conclusion, C3H-D2KO mice have notably elevated serum T 4 levels, and this, in conjunction with residual D1 activity, is likely an important role in the maintenance of euthyroid serum T3 concentrations.

AB - For T3 to mediate its biological effects, the prohormone T 4 must be activated by removal of an outer-ring iodine by the type 1 or 2 deiodinases (D1 and D2) with approximately 60% of the daily T3 production in rodents being produced extrathyroidally through this pathway. To further define the role of these enzymes in thyroid hormone homeostasis, we backcrossed the targeted disruption of the Dio2 gene into C3H/HeJ (C3H) mice with genetically low D1 expression to create the C3H-D2KO mouse. Remarkably, these mice maintain euthyroid serum T3 levels with normal growth and no decrease in expression of hepatic T3-responsive genes. However, serum T4 is increased 1.2-fold relative to the already elevated C3H levels, and serum TSH is increased 1.4-fold. Despite these increases, thyroidal 125I uptake indicates no difference in thyroidal activity between C3H-D2KO and C3H mice. Although C3H-D2KO hepatic and renal D1 activities were well below those observed in wild-type mice (∼0.1-fold for both), they were 8-fold and 2-fold higher, respectively, relative to C3H mice. Thyroidal D1 and cerebral cortical type 3 deiodinase activity were unchanged between C3H-D2KO and C3H mice. In conclusion, C3H-D2KO mice have notably elevated serum T 4 levels, and this, in conjunction with residual D1 activity, is likely an important role in the maintenance of euthyroid serum T3 concentrations.

UR - http://www.scopus.com/inward/record.url?scp=33847055555&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33847055555&partnerID=8YFLogxK

U2 - 10.1210/en.2006-1042

DO - 10.1210/en.2006-1042

M3 - Article

C2 - 17138654

AN - SCOPUS:33847055555

VL - 148

SP - 954

EP - 960

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 3

ER -