Involvement of T3Rα- and β-receptor subtypes in mediation of T3 functions during postnatal murine intestinal development

Involvement of T3Rα- and β-receptor subtypes in mediation of T3 functions during postnatal murine intestinal development

Background & Aims: Thyroid hormones are implicated in intestinal development. Their effects are mediated by nuclear receptors, which are transcriptional regulators activated upon binding of triiodothyronine. The aim of this study was to define the involvement of the receptor subtypes during inte...

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Veröffentlicht in:Gastroenterology (New York, N.Y. 1943) N.Y. 1943), 1999, Vol.116 (6), p.1367-1378
Hauptverfasser: Plateroti, Michelina, Chassande, Olivier, Fraichard, Alexandre, Gauthier, Karine, Freund, Jean–Noël, Samarut, Jacques, Kedinger, Michèle
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container_end_page 1378
container_issue 6
container_start_page 1367
container_title Gastroenterology (New York, N.Y. 1943)
container_volume 116
creator Plateroti, Michelina
Chassande, Olivier
Fraichard, Alexandre
Gauthier, Karine
Freund, Jean–Noël
Samarut, Jacques
Kedinger, Michèle
description Background & Aims: Thyroid hormones are implicated in intestinal development. Their effects are mediated by nuclear receptors, which are transcriptional regulators activated upon binding of triiodothyronine. The aim of this study was to define the involvement of the receptor subtypes during intestinal development. Methods: We used strains of knockout mice lacking T3Rα, T3Rβ, or both receptors, encoded by T3Rα and T3Rβ genes. Results: Morphological features and expression of digestive enzymes and of two intestinal regulators, Cdx-1 and Cdx-2, were compared in wild-type and T3Rα, T3Rβ, and T3Rαβ knockout animals. T3Rα−/− mice had abnormal intestinal morphology, assessed by a decrease in the number of epithelial cells along the crypt-villus axis and a decrease in proliferating crypt cells. Expression of Cdx-1 and Cdx-2, and of the digestive enzymes, was down-regulated. These parameters can be partially reversed by T3 injection. A similar (jejunum) or more severe (ileum) phenotype was found in T3Rαβ double mutants. In contrast, no changes occurred in T3Rβ mice. Conclusions: These data describe for the first time a direct effect of TH through the T3Rα-receptor subtypes on postnatal intestinal mucosa maturation. They also suggest that T3Rβ receptors are dispensable but can partially substitute for T3Rα. GASTROENTEROLOGY 1999;116:1367-1378
doi_str_mv 10.1016/S0016-5085(99)70501-9
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Their effects are mediated by nuclear receptors, which are transcriptional regulators activated upon binding of triiodothyronine. The aim of this study was to define the involvement of the receptor subtypes during intestinal development. Methods: We used strains of knockout mice lacking T3Rα, T3Rβ, or both receptors, encoded by T3Rα and T3Rβ genes. Results: Morphological features and expression of digestive enzymes and of two intestinal regulators, Cdx-1 and Cdx-2, were compared in wild-type and T3Rα, T3Rβ, and T3Rαβ knockout animals. T3Rα−/− mice had abnormal intestinal morphology, assessed by a decrease in the number of epithelial cells along the crypt-villus axis and a decrease in proliferating crypt cells. Expression of Cdx-1 and Cdx-2, and of the digestive enzymes, was down-regulated. These parameters can be partially reversed by T3 injection. A similar (jejunum) or more severe (ileum) phenotype was found in T3Rαβ double mutants. In contrast, no changes occurred in T3Rβ mice. Conclusions: These data describe for the first time a direct effect of TH through the T3Rα-receptor subtypes on postnatal intestinal mucosa maturation. They also suggest that T3Rβ receptors are dispensable but can partially substitute for T3Rα. 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Their effects are mediated by nuclear receptors, which are transcriptional regulators activated upon binding of triiodothyronine. The aim of this study was to define the involvement of the receptor subtypes during intestinal development. Methods: We used strains of knockout mice lacking T3Rα, T3Rβ, or both receptors, encoded by T3Rα and T3Rβ genes. Results: Morphological features and expression of digestive enzymes and of two intestinal regulators, Cdx-1 and Cdx-2, were compared in wild-type and T3Rα, T3Rβ, and T3Rαβ knockout animals. T3Rα−/− mice had abnormal intestinal morphology, assessed by a decrease in the number of epithelial cells along the crypt-villus axis and a decrease in proliferating crypt cells. Expression of Cdx-1 and Cdx-2, and of the digestive enzymes, was down-regulated. These parameters can be partially reversed by T3 injection. A similar (jejunum) or more severe (ileum) phenotype was found in T3Rαβ double mutants. In contrast, no changes occurred in T3Rβ mice. Conclusions: These data describe for the first time a direct effect of TH through the T3Rα-receptor subtypes on postnatal intestinal mucosa maturation. They also suggest that T3Rβ receptors are dispensable but can partially substitute for T3Rα. 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title Involvement of T3Rα- and β-receptor subtypes in mediation of T3 functions during postnatal murine intestinal development
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