Replacement therapy for hypothyroidism with thyroxine alone does not ensure euthyroidism in all tissues, as studied in thyroidectomized rats.

Escobar‐Morreale, Héctor F.; Obregón, Marı́a Jesús; Rey, Francisco Escobar del; Escobar, Gabriella Morreale de

doi:10.1172/jci118353

Cited by 255 publications

(200 citation statements)

References 47 publications

Supporting

Mentioning

180

Contrasting

Unclassified

Order By: Relevance

“…Notably, a slightly lower dose of T 3 , 2.0 ng/g BW, has been shown to restore growth and the activity of liver a-GPD in previously rendered hypothyroid rats (202). However, administration of T 3 alone is not sufficient to restore euthyroidism in all tissues, particularly in those with a significant contribution of the D2 pathway (243,244).…”

Section: And Recommendation 24amentioning

confidence: 98%

“…However, in rats L-T 4 monotherapy cannot simultaneously normalize serum T 3 , T 4 , and TSH, presumably because of the higher thyroidal T 3 production in rodents (243,244). Thus to normalize T 3 and TSH, the serum T 4 must be higher than normal in rats, and the same applies to tissue T 3 and T 4 content.…”

Section: [E2] Thyroid Hormone Replacement In Animalsmentioning

confidence: 99%

“…Some studies have established the optimal dosing for combination therapy in rodents (244). When T 4 is used alone for replacement, tissue T 3 content can vary across a large number of tissues because of the role played by the deiodinases as a local source of tissue T 3 (via conversion from T 4 ) (243,244).…”

Section: And Recommendation 24amentioning

confidence: 99%

“…While food-and water-based drug delivery methods are subject to feeding variability, this may not be critical for studies of chronic thyrotoxicosis; for example, powdered rodent diet containing 3 mg of T 4 and 1 mg of T 3 per kilogram has been used successfully to induce chronic thyrotoxicosis (205). Consideration should be given to more consistent methods such as subcutaneous pumps or pellets (243,244).…”

Section: [F1] Thyrotoxicosis In Animalsmentioning

confidence: 99%

See 3 more Smart Citations

American Thyroid Association Guide to Investigating Thyroid Hormone Economy and Action in Rodent and Cell Models

Bianco

Anderson

Forrest

et al. 2014

Thyroid

167

106

View full text Add to dashboard Cite

Section: And Recommendation 24amentioning

confidence: 98%

Section: [E2] Thyroid Hormone Replacement In Animalsmentioning

confidence: 99%

Section: And Recommendation 24amentioning

confidence: 99%

Section: [F1] Thyrotoxicosis In Animalsmentioning

confidence: 99%

See 2 more Smart Citations

American Thyroid Association Guide to Investigating Thyroid Hormone Economy and Action in Rodent and Cell Models

Bianco

Anderson

Forrest

et al. 2014

Thyroid

167

106

View full text Add to dashboard Cite

“…Until now, evidence suggesting that TH influences adult lung physiology has been indirect and based on the presence of TH receptors (8), deiodinases (9)(10)(11)(12), and measured TH concentrations (10,13,14) in the lung.…”

mentioning

confidence: 99%

Role of type 2 deiodinase in response to acute lung injury (ALI) in mice

Barca-Mayo

Liao

DiCosmo

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Thyroid hormone (TH) metabolism, mediated by deiodinase types 1, 2, and 3 (D1, D2, and D3) is profoundly affected by acute illness. We examined the role of TH metabolism during ventilator-induced lung injury (VILI) in mice. Mice exposed to VILI recapitulated the serum TH findings of acute illness, namely a decrease in 3,5,3′-triiodothyronine (T 3 ) and thyroid-stimulating hormone and an increase in reverse T 3 . Both D2 immunoreactivity and D2 enzymatic activity were increased significantly. D1 and D3 activity did not change. Using D2 knockout (D2KO) mice, we determined whether the increase in D2 was an adaptive response. Although similar changes in serum TH levels were observed in D2KO and WT mice, D2KO mice exhibited greater susceptibility to VILI than WT mice, as evidenced by poorer alveoli integrity and quantified by lung chemokine and cytokine mRNA induction. These data suggest that an increase in lung D2 is protective against VILI. Similar findings of increased inflammatory markers were found in hypothyroid WT mice exposed to VILI compared with euthyroid mice, indicating that the lungs were functionally hypothyroid. Treatment of D2KO mice with T 3 reversed many of the lung chemokine and cytokine profiles seen in response to VILI, demonstrating a role for T 3 in the treatment of lung injury. We conclude that TH metabolism in the lung is linked to the response to inflammatory injury and speculate that D2 exerts its protective effect by making more TH available to the injured lung tissue.nonthyroidal illness | euthyroid sick | reverse triiodothyronine | bronchial alveolar lavage | sepsis T hyroid hormone [TH, here denoting the active hormone 3,5,3′-triiodothyronine (T 3 ) and its precursor thyroxine (T 4 )] is necessary for the normal development and function of virtually every vertebrate tissue. Although the thyroid gland is predominantly responsible for the production and release of T 4 , the cellular bioavailability of the active T 3 depends on TH-specific transporters and tissue TH metabolism. Metabolism of TH is regulated by three iodothyronine deiodinases. Both type 1 (D1) and type 2 (D2) deiodinases serve to generate bioactive T 3 by outer-ring deiodination of T 4 . D2 has a major role in the intracellular generation of the active TH in mouse; the role of the D1, with its broad substrate specificity and ability to carry out both outer-and inner-ring deiodination, is less well understood. In contrast, type 3 iodothyronine deiodinase (D3) inactivates TH by inner-ring deiodination of T 4 to reverse T 3 (3′,5,3-triiodothyronine; rT 3 ) and T 3 to 3,3′-diiodothyronine (T 2 ), both biologically inactive compounds (1).Studies have elucidated the dynamic effects of TH action on brain, bone, liver (2-5), and maturation of the fetal lung (6, 7), but little is known regarding the role of TH in adult lung physiology. Until now, evidence suggesting that TH influences adult lung physiology has been indirect and based on the presence of TH receptors (8), deiodinases (9-12), and measured TH concentrations (10,13,14) i...

show abstract