Generation of thyrotropin-releasing hormone receptor 1-deficient mice as an animal model of central hypothyroidism

Roland Rabeler, Jens Mittag, Lars Geffers, Ulrich Rüther, Michael Leitges, Albert F Parlow, Theo J Visser, Karl Bauer

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70 Citations (Scopus)

Abstract

To provide an animal model of central hypothyroidism, mice deficient in the TRH-receptor 1 (TRH-R1) gene were generated by homologous recombination. The pituitaries of TRH-R1-/- mice are devoid of any TRH-binding capacity, demonstrating that TRH-R1 is the only receptor localized on TRH target cells of the pituitary. With the exception of some retardation in growth rate, TRH-R1-/- mice appear normal, but compared with control animals they exhibit a considerable decrease in serum T(3), T(4), and prolactin (PRL) levels but not in serum TSH levels. In situ hybridization histochemistry and real-time RT-PCR analysis revealed that in adult TRH-R1-/- animals TSHbeta-mRNA expression is not impaired whereas PRL mRNA and GH mRNA levels are considerably reduced compared with control mice. The numbers of thyrotropes, somatotropes, and lactotropes, however, are not affected by the deletion of the TRH-R1 gene. The mutant mice are fertile, and the dams nourish their pups well, indicating that TRH is not a decisive factor for suckling-induced PRL release. In situ hybridization and quantitative RT-PCR analysis, furthermore, revealed that, as in control animals, pituitary PRL-mRNA expression in TRH-R1-/- is considerably increased during lactation, albeit strongly reduced as compared with lactating control animals.

Original languageEnglish
Pages (from-to)1450-60
Number of pages11
JournalMolecular endocrinology (Baltimore, Md.)
Volume18
Issue number6
DOIs
Publication statusPublished - Jun 2004
Externally publishedYes

Keywords

  • Animals
  • Blotting, Northern
  • Blotting, Southern
  • Disease Models, Animal
  • Female
  • Genetic Vectors
  • Genotype
  • Growth Hormone/metabolism
  • Hypothyroidism/genetics
  • In Situ Hybridization
  • Lac Operon
  • Lactation
  • Male
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Models, Genetic
  • Mutation
  • Pituitary Gland/metabolism
  • Pituitary Hormones/metabolism
  • Polymerase Chain Reaction
  • Prolactin/blood
  • RNA, Messenger/metabolism
  • Receptors, Thyrotropin-Releasing Hormone/genetics
  • Recombination, Genetic
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thyrotropin-Releasing Hormone/blood
  • Thyroxine/blood
  • Time Factors
  • Transcription, Genetic
  • Triiodothyronine/blood

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