Absence of thyroid hormone receptor β–retinoid X receptor interactions in auditory function and in the pituitary–thyroid axis
1998; Lippincott Williams & Wilkins; Volume: 9; Issue: 13 Linguagem: Inglês
10.1097/00001756-199809140-00003
ISSN1473-558X
AutoresÁngel Campos‐Barros, Lawrence C. Erway, Wojciech Krężel, Tom Curran, Philippe Kastner, Pierre Chambon, Douglas Forrest,
Tópico(s)Biochemical Analysis and Sensing Techniques
ResumoTHYROID hormone receptor β–deficient (TRβ–/–) mice have defective auditory-evoked brain stem responses (ABR). Since in vitro, TRβ binds to DNA as homodimers or as heterodimers with retinoid X receptors (RXRs), we investigated whether the TRβ–/– phenotype may reflect loss of RXR-TRβ heterodimer or TRβ homo-dimer function. Normal ABR thresholds were recorded in RXRβ–/–, RXRγ–/– RXRα–/+ and RXR compound mutant mice. When RXR mutations were introduced onto TRβ–/+ or TR–/– backgrounds, thresholds were dictated solely by TRβ and not RXR genotype. TRβ–/– mice also over-produce thyroid hormones and thyroid stimulating hormone; however, levels of these hormones were unaltered by RXR mutations. This suggests that, contrary to in vitro models, RXRs may be dispensable and that TRβ may function in vivo by an RXR-independent mechanism in the auditory system and pituitary–thyroid axis.
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