Coordination of hypothalamic and pituitary T3 production regulates TSH expression

Tatiana L. Fonseca, Mayrin Correa-Medina, Maira P O Campos, Gabor Wittmann, Joao P. Werneck-de-Castro, Rafael Arrojoe Drigo, Magda Mora-Garzon, Cintia Bagne Ueta, Diego A Caicedo-Vierkant, Csaba Fekete, Balazs Gereben, Ronald M. Lechan, Antonio C. Bianco

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

Type II deiodinase (D2) activates thyroid hormone by converting thyroxine (T4) to 3,5,3'-triiodothyronine (T3). This allows plasma T4 to signal a negative feedback loop that inhibits production of thyrotropin-releasing hormone (TRH) in the mediobasal hypothalamus (MBH) and thyroid-stimulating hormone (TSH) in the pituitary. To determine the relative contributions of these D2 pathways in the feedback loop, we developed 2 mouse strains with pituitary- and astrocyte-specific D2 knockdown (pit-D2 KO and astro-D2 KO mice, respectively). The pit-D2 KO mice had normal serum T3 and were systemically euthyroid, but exhibited an approximately 3-fold elevation in serum TSH levels and a 40% reduction in biological activity. This was the result of elevated serum T4 that increased D2-mediated T3 production in the MBH, thus decreasing Trh mRNA. That tanycytes, not astrocytes, are the cells within the MBH that mediate T4-to-T3 conversion was defined by studies using the astro-D2 KO mice. Despite near-complete loss of brain D2, tanycyte D2 was preserved in astro-D2 KO mice at levels that were sufficient to maintain both the T4-dependent negative feedback loop and thyroid economy. Taken together, these data demonstrated that the hypothalamic-thyroid axis is wired to maintain normal plasma T3 levels, which is achieved through coordination of T4-to-T3 conversion between thyrotrophs and tanycytes.

Original languageEnglish
Pages (from-to)1492-1500
Number of pages9
JournalJournal of Clinical Investigation
Volume123
Issue number4
DOIs
StatePublished - Apr 1 2013

Fingerprint

Thyrotropin
Hypothalamus
Ependymoglial Cells
Astrocytes
Thyroid Gland
Serum
Thyrotrophs
Iodide Peroxidase
Thyrotropin-Releasing Hormone
Triiodothyronine
Thyroxine
Thyroid Hormones
Messenger RNA
Brain

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Fonseca, T. L., Correa-Medina, M., Campos, M. P. O., Wittmann, G., Werneck-de-Castro, J. P., Drigo, R. A., ... Bianco, A. C. (2013). Coordination of hypothalamic and pituitary T3 production regulates TSH expression. Journal of Clinical Investigation, 123(4), 1492-1500. https://doi.org/10.1172/JCI61231

Coordination of hypothalamic and pituitary T3 production regulates TSH expression. / Fonseca, Tatiana L.; Correa-Medina, Mayrin; Campos, Maira P O; Wittmann, Gabor; Werneck-de-Castro, Joao P.; Drigo, Rafael Arrojoe; Mora-Garzon, Magda; Ueta, Cintia Bagne; Caicedo-Vierkant, Diego A; Fekete, Csaba; Gereben, Balazs; Lechan, Ronald M.; Bianco, Antonio C.

In: Journal of Clinical Investigation, Vol. 123, No. 4, 01.04.2013, p. 1492-1500.

Research output: Contribution to journalArticle

Fonseca, TL, Correa-Medina, M, Campos, MPO, Wittmann, G, Werneck-de-Castro, JP, Drigo, RA, Mora-Garzon, M, Ueta, CB, Caicedo-Vierkant, DA, Fekete, C, Gereben, B, Lechan, RM & Bianco, AC 2013, 'Coordination of hypothalamic and pituitary T3 production regulates TSH expression', Journal of Clinical Investigation, vol. 123, no. 4, pp. 1492-1500. https://doi.org/10.1172/JCI61231
Fonseca TL, Correa-Medina M, Campos MPO, Wittmann G, Werneck-de-Castro JP, Drigo RA et al. Coordination of hypothalamic and pituitary T3 production regulates TSH expression. Journal of Clinical Investigation. 2013 Apr 1;123(4):1492-1500. https://doi.org/10.1172/JCI61231
Fonseca, Tatiana L. ; Correa-Medina, Mayrin ; Campos, Maira P O ; Wittmann, Gabor ; Werneck-de-Castro, Joao P. ; Drigo, Rafael Arrojoe ; Mora-Garzon, Magda ; Ueta, Cintia Bagne ; Caicedo-Vierkant, Diego A ; Fekete, Csaba ; Gereben, Balazs ; Lechan, Ronald M. ; Bianco, Antonio C. / Coordination of hypothalamic and pituitary T3 production regulates TSH expression. In: Journal of Clinical Investigation. 2013 ; Vol. 123, No. 4. pp. 1492-1500.
@article{d0974cdadca24618b71f109d9165a40a,
title = "Coordination of hypothalamic and pituitary T3 production regulates TSH expression",
abstract = "Type II deiodinase (D2) activates thyroid hormone by converting thyroxine (T4) to 3,5,3'-triiodothyronine (T3). This allows plasma T4 to signal a negative feedback loop that inhibits production of thyrotropin-releasing hormone (TRH) in the mediobasal hypothalamus (MBH) and thyroid-stimulating hormone (TSH) in the pituitary. To determine the relative contributions of these D2 pathways in the feedback loop, we developed 2 mouse strains with pituitary- and astrocyte-specific D2 knockdown (pit-D2 KO and astro-D2 KO mice, respectively). The pit-D2 KO mice had normal serum T3 and were systemically euthyroid, but exhibited an approximately 3-fold elevation in serum TSH levels and a 40{\%} reduction in biological activity. This was the result of elevated serum T4 that increased D2-mediated T3 production in the MBH, thus decreasing Trh mRNA. That tanycytes, not astrocytes, are the cells within the MBH that mediate T4-to-T3 conversion was defined by studies using the astro-D2 KO mice. Despite near-complete loss of brain D2, tanycyte D2 was preserved in astro-D2 KO mice at levels that were sufficient to maintain both the T4-dependent negative feedback loop and thyroid economy. Taken together, these data demonstrated that the hypothalamic-thyroid axis is wired to maintain normal plasma T3 levels, which is achieved through coordination of T4-to-T3 conversion between thyrotrophs and tanycytes.",
author = "Fonseca, {Tatiana L.} and Mayrin Correa-Medina and Campos, {Maira P O} and Gabor Wittmann and Werneck-de-Castro, {Joao P.} and Drigo, {Rafael Arrojoe} and Magda Mora-Garzon and Ueta, {Cintia Bagne} and Caicedo-Vierkant, {Diego A} and Csaba Fekete and Balazs Gereben and Lechan, {Ronald M.} and Bianco, {Antonio C.}",
year = "2013",
month = "4",
day = "1",
doi = "10.1172/JCI61231",
language = "English",
volume = "123",
pages = "1492--1500",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "4",

}

TY - JOUR

T1 - Coordination of hypothalamic and pituitary T3 production regulates TSH expression

AU - Fonseca, Tatiana L.

AU - Correa-Medina, Mayrin

AU - Campos, Maira P O

AU - Wittmann, Gabor

AU - Werneck-de-Castro, Joao P.

AU - Drigo, Rafael Arrojoe

AU - Mora-Garzon, Magda

AU - Ueta, Cintia Bagne

AU - Caicedo-Vierkant, Diego A

AU - Fekete, Csaba

AU - Gereben, Balazs

AU - Lechan, Ronald M.

AU - Bianco, Antonio C.

PY - 2013/4/1

Y1 - 2013/4/1

N2 - Type II deiodinase (D2) activates thyroid hormone by converting thyroxine (T4) to 3,5,3'-triiodothyronine (T3). This allows plasma T4 to signal a negative feedback loop that inhibits production of thyrotropin-releasing hormone (TRH) in the mediobasal hypothalamus (MBH) and thyroid-stimulating hormone (TSH) in the pituitary. To determine the relative contributions of these D2 pathways in the feedback loop, we developed 2 mouse strains with pituitary- and astrocyte-specific D2 knockdown (pit-D2 KO and astro-D2 KO mice, respectively). The pit-D2 KO mice had normal serum T3 and were systemically euthyroid, but exhibited an approximately 3-fold elevation in serum TSH levels and a 40% reduction in biological activity. This was the result of elevated serum T4 that increased D2-mediated T3 production in the MBH, thus decreasing Trh mRNA. That tanycytes, not astrocytes, are the cells within the MBH that mediate T4-to-T3 conversion was defined by studies using the astro-D2 KO mice. Despite near-complete loss of brain D2, tanycyte D2 was preserved in astro-D2 KO mice at levels that were sufficient to maintain both the T4-dependent negative feedback loop and thyroid economy. Taken together, these data demonstrated that the hypothalamic-thyroid axis is wired to maintain normal plasma T3 levels, which is achieved through coordination of T4-to-T3 conversion between thyrotrophs and tanycytes.

AB - Type II deiodinase (D2) activates thyroid hormone by converting thyroxine (T4) to 3,5,3'-triiodothyronine (T3). This allows plasma T4 to signal a negative feedback loop that inhibits production of thyrotropin-releasing hormone (TRH) in the mediobasal hypothalamus (MBH) and thyroid-stimulating hormone (TSH) in the pituitary. To determine the relative contributions of these D2 pathways in the feedback loop, we developed 2 mouse strains with pituitary- and astrocyte-specific D2 knockdown (pit-D2 KO and astro-D2 KO mice, respectively). The pit-D2 KO mice had normal serum T3 and were systemically euthyroid, but exhibited an approximately 3-fold elevation in serum TSH levels and a 40% reduction in biological activity. This was the result of elevated serum T4 that increased D2-mediated T3 production in the MBH, thus decreasing Trh mRNA. That tanycytes, not astrocytes, are the cells within the MBH that mediate T4-to-T3 conversion was defined by studies using the astro-D2 KO mice. Despite near-complete loss of brain D2, tanycyte D2 was preserved in astro-D2 KO mice at levels that were sufficient to maintain both the T4-dependent negative feedback loop and thyroid economy. Taken together, these data demonstrated that the hypothalamic-thyroid axis is wired to maintain normal plasma T3 levels, which is achieved through coordination of T4-to-T3 conversion between thyrotrophs and tanycytes.

UR - http://www.scopus.com/inward/record.url?scp=84875830148&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84875830148&partnerID=8YFLogxK

U2 - 10.1172/JCI61231

DO - 10.1172/JCI61231

M3 - Article

VL - 123

SP - 1492

EP - 1500

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 4

ER -