The syndromes of resistance to thyroid hormone
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- "Impaired tyrosine sulfation of TSH receptor molecules by inactivation of TPST2 reduces responsiveness to TSH and causes the functional failure of the thyroid in grt mice . Thyroid hormone (TH) functions in many critical aspects of brain development, including synaptic formation , neuronal migration , and glial myelination , and, consequently, TH deficiency causes mental retardation . Interestingly hypothyroid rats display a decrease in the number of PV-positive interneurons , and this phenomenon is reversed by treatment with TH . "
ABSTRACT: Thyroid hormone (TH) plays an important role in brain development, and TH deficiency during pregnancy or early postnatal periods leads to neurological disorders such as cretinism. Hypothyroidism reduces the number of parvalbumin (PV)-positive interneurons in the neocortex and hippocampus. Here we used a mouse strain (growth-retarded; grt) that shows growth retardation and hypothyroidism to examine whether somatostatin (Sst)-positive interneurons that are generated from the same pool of neural progenitor cells as PV-positive cells are also altered by TH deficiency. The number of PV-positive interneurons was significantly decreased in the neocortex and hippocampus of grt mice as compared with normal control mice. In contrast to the decrease in the number of PV neurons, the number of Sst-positive interneurons in grt mice was increased in the stratum oriens of the hippocampus and the hilus of the dentate gyrus, although their number was unchanged in the neocortex. These changes were reversed by triiodothyronine administration from postnatal day (PD) 0 to 20. TH supplementation that was initiated after PD21 did not, however, affect the number of PV- or Sst-positive cells. These results suggest that during the first three postnatal weeks, TH may be critical for the generation of subpopulations of interneurons.Neuroscience Letters 12/2013; 559. DOI:10.1016/j.neulet.2013.11.052 · 2.06 Impact Factor
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- "This critical period is when TH is essential for development of normal hearing (Knipper et al., 2001). Deafness in humans and mice related to TR dysfunction has been associated with a deficiency of TRb (Forrest et al., 1996a; Refetoff et al., 1993), whereas TRa1 knockout mice do not show hearing loss (Forrest et al., 1996a, 1996b; Rüsch et al., 1998). However, auditory defects have been reported recently in mice with a TRa1 point mutation, which were proposed to result from bone ossification defects of the ossicles (Cordas et al., 2012). "
ABSTRACT: Thyroid hormone acts on gene transcription by binding to its nuclear receptors TRα1 and TRβ. Whereas global deletion of TRβ causes deafness, global TRα-deficient mice have normal hearing thresholds. Since the individual roles of the two receptors in cochlear hair cells are still unclear, we generated mice with a hair cell-specific mutation of TRα1 or deletion of TRβ using the Cre-loxP system. Hair cell-specific TRβ mutant mice showed normal hearing thresholds but delayed BK channel expression in inner hair cells, slightly stronger outer hair cell function, and slightly reduced amplitudes of auditory brainstem responses. In contrast, hair cell-specific TRα mutant mice showed normal timing of BK channel expression, slightly reduced outer hair cell function, and slightly enhanced amplitudes of auditory brainstem responses. Our data demonstrate that TRβ-related deafness originates outside of hair cells and that TRα and TRβ play opposing, non-redundant roles in hair cells. A role for thyroid hormone receptors in controlling key regulators that shape signal transduction during development is discussed. Thyroid hormone may act through different thyroid hormone receptor activities to permanently alter the sensitivity of auditory neurotransmission.Molecular and Cellular Endocrinology 09/2013; 382(1). DOI:10.1016/j.mce.2013.08.025 · 4.24 Impact Factor
Contemporary Aspects of Endocrinology, 11/2011; , ISBN: 978-953-307-357-6
- "Although linkage analysis of these patients showed no relation with NCoR, SMRT, SRC-1 or RXRγ (Reutrakul et al., 2000), an understanding of the transcriptional control mechanisms underlying non-TR RTH may provide an insight into the molecular basis of negative regulation of the TSHβ gene. Second, RTH is clinically classified as a generalized resistance to thyroid hormone (GRTH) and resistance of the pituitary to thyroid hormone (PRTH) (Refetoff et al., 1993). Patients with PRTH possess mutations similar or identical to those found in GRTH; however, PRTH patients display greater resistance to thyroid hormone in thyrotrophs compared to peripheral tissues, resulting in thyrotoxicosis. "