Responses of the Thyroid Gland to TSH and Other Thyroid Stimulators in the Growth-Retarded (<i>grt</i>) Mouse

Kobayashi, Kenichi; Yamamoto, Hideaki; Kobayashi, Tetsuya; Machida, Takeo

doi:10.2108/zsj.18.955

Cited by 11 publications

(26 citation statements)

References 25 publications

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Section: Introductionmentioning

confidence: 99%

“…In grt mice, plasma concentrations of thyroxine (T 4 ) are significantly lower, whereas levels of thyroid-stimulating hormone (TSH) are greatly elevated (Yoshida et al 1994, Tomita et al 1995, Kobayashi et al 2001. The unresponsive nature of TSH receptors to TSH is considered to be attributable to dysfunction of the grt thyroid gland (Kobayashi et al 2001(Kobayashi et al , 2005. Recently, the grt phenotype has been shown to be caused by a single missense mutation in the tyrosylprotein sulfotransferase 2 (Tpst2) gene with a C-to-G transition at nucleotide 798, leading to replacement of a highly conserved histidine with glutamine at codon 266 in the sulfotransferase domain (Sasaki et al 2007).…”

Section: Introductionmentioning

confidence: 99%

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Impaired insulin secretion from the pancreatic islets of hypothyroidal growth-retarded mice

Taguchi¹,

Tasaki²,

Terakado³

et al. 2010

Journal of Endocrinology

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The growth-retarded (grt) mouse shows thyroid dysfunctionrelated hyporesponsiveness to TSH. Thyroid hormone is a critical regulator of metabolism in many cells; thus, derangement of thyroid function affects many organs and systems. Experiments were conducted focusing on the function of the pancreatic islets in grt mice. We showed occurrence of a fasting hyperglycemia and a decreased plasma insulin level response to a glucose load in grt mice, despite normal insulin molecules being stored in secretory granules of pancreatic islets. We also demonstrated a reduction of insulin secretion in response to glucose administration from islets of grt mice in vitro, while the insulin release in response to KCl stimulation was comparable to that in normal mice, indicating that the isolated islets from grt mice have normal ATPsensitive K C channels and postchannel activity. The mRNA expression levels of glucose transporter 2 and glucokinase in the islets of grt mice were similar to those in normal mice. Triiodothyronine administration to grt mice improved insulin secretion very slightly. On the other hand, mRNA for tyrosylprotein sulfotransferase 2 (Tpst2) was found to be expressed in the pancreatic islets of grt mice. Considering that Tpst2 is the responsible gene of grt mice, mutation of which is associated with a poor function of TSH receptor, the findings raise a possibility of involvement of factors including Tpst2 in the insulin hyposecretion in grt mice.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Impaired insulin secretion from the pancreatic islets of hypothyroidal growth-retarded mice

Taguchi¹,

Tasaki²,

Terakado³

et al. 2010

Journal of Endocrinology

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“…In grt mice, plasma concentrations of thyroxine are significantly lower, whereas levels of thyroid-stimulating hormone (TSH) are greatly elevated [12,15]. Our previous reports suggested that TSH can bind to its receptor in the grt thyroid gland, but is incapable of activating the second messenger signaling pathway [9,10]. A mapping study indicated that the grt locus is located on mouse chromosome 5 and a mutation in the TSH receptor gene is unlikely to be responsible for the grt genotype [1].…”

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confidence: 99%

Testicular Development in Growth-Retarded Mice

2007

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Abstract:To assess delayed fertility in male growth-retarded (grt) The growth-retarded (grt) mouse was first reported as a mutant spontaneously derived from phenotypically normal siblings of the Snell's dwarf mouse (DW/J strain) with characteristic growth pause followed by delayed onset of pubertal growth in contrast to dw mice [15]. In grt mice, plasma concentrations of thyroxine are significantly lower, whereas levels of thyroid-stimulating hormone (TSH) are greatly elevated [12,15]. Our previous reports suggested that TSH can bind to its receptor in the grt thyroid gland, but is incapable of activating the second messenger signaling pathway [9,10]. A mapping study indicated that the grt locus is located on mouse chromosome 5 and a mutation in the TSH receptor gene is unlikely to be responsible for the grt genotype [1].We noticed that male grt mice are infertile at the young adult stage (~13 weeks), but their fertility is partially restored after 26 weeks [8]. To understand the (Received 13 April 2007 / Accepted 19 July 2007 Address corresponding : K. Kobayashi, National Institute of Occupational Safety and Health, Kawasaki, Japan delayed maturity of testes in grt mice, we compared testicular development with that of phenotypically normal littermates.A colony of grt mice was originally maintained at the animal facility at Saitama University (Saitama, Japan) under conventional conditions. An SPF colony of grt mice was established at Japan Laboratory Animals, Inc. (Tokyo, Japan) and then, they were introduced to our animal facility. The mice were kept in a semibarrier system with a controlled environment (temperature: 23 ± 2°C; humidity: 55 ± 10%; lighting: 12-h light/dark cycle) throughout the study. A standard laboratory diet (CE-2, CLEA Japan Inc., Tokyo, Japan) and tap water were available ad libitum. Normal phenotype (+/+ or +/grt) and growth-retarded (grt/ grt) male mice were obtained by mating wild (+/+) or heterozygous (+/grt) female mice with grt male siblings [9]. Normal and grt mice were distinguished on

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“…Such brain hypoplasia was attributed to a region-specific lower volume of the grt/grt cerebrum by two-way ANOVA and post-hoc testing (P < 0.001) (Fig. 1D).While grt/grt mice have a defect in tyrosylprotein sulfotransferase 2 (Tpst2) gene, the cerebral volume reduction revealed in the present volumetric analysis may be rather involved in the hypothyroid status of grt/grt mice (Kobayashi et al 2001), because similar cerebral hypoplasia is obtained by experimentallyinduced hypothyroid rats (Madeira et al 1990). Thus, CT-or MRIbased volumetry can be screened changes in brain structures of small laboratory animal models.…”

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confidence: 70%

Brain volumetry: A quantitative approach for detecting region‐specific structural abnormalities

Sawada

Saito

Horiuchi-Hirose

et al. 2015

Congenital Anomalies

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Dear Editor, In recent years, the conspicuous development and spread of imaging techniques, i.e. magnetic resonance imaging (MRI) and computed tomography (CT), have allowed non-invasive investigation of the three-dimensional (3D) gross anatomical structures of the brain. Volumetry is a quantitative approach using imaging techniques for detecting structural differences in organs among two or more groups. In our recent study, T2-weighted MRI-based volumetry revealed a dose-dependent volume reduction of the whole cerebellum by prenatal exposure to a single whole body X-irradiation in rats (Sawada et al. 2013). Here, we attempted the CT-based volumetry of the brain of a growth-retarded mouse (grt/ grt), which is known as an animal model for primary congenital hypothyroidism (Sasaki et al. 2007).Brains from male homozygous (grt/grt, n = 5) and heterogeneous (grt/+, n = 5) mice at 15 weeks of age were soaked in 150 mg/mL nonionic iodinated contrast agent (Iopamiron, Bayer Schering Pharma, Japan) in a 7.5% paraformaldehyde solution at 4°C for 14 days to achieve a better contrast of the white and gray matter structures in inverted images by ex vivo micro-CT (Saito and Murase 2012). Then, CT images were acquired using 3D micro-CT (RmCT, Rigaku, Tokyo, Japan) with a resolution of 39 × 39 × 39 μm 3 , a tube voltage peak of 90 kV, and a tube current of 200 μA with a scan time of 8 min. Brain regions, i.e. the cerebrum, diencephalon, midbrain, pons, medulla oblongata and cerebellum, were semi-automatically segmented on CT images using the "Morpho" tool of SliceOmatic software ver 4.3 (TomoVision, Montreal, Canada) based on image contrast as well as the user's knowledge of the anatomy. 3D-rendered images of the brain were constructed using those segmented images. Furthermore, segmented areas of each brain region were measured, and the volumes were calculated by multiplying the combined areas by the slice thickness (39 μm). The total volume of segmented regions was regarded as the whole-brain volume.Computed tomography images could distinguish gray and white matter structures by their contrast, and the brain regions were grossly identifiable (Fig. 1A). 3D-rendered images revealed no obvious difference in the 3D morphology and structural organization of the brain between grt/grt and grt/ + (Fig. 1B). The volume of whole-brain was calculated based on CT images. A significantly decreased brain volume was noted in grt/grt (P < 0.05) (Fig. 1C). Such brain hypoplasia was attributed to a region-specific lower volume of the grt/grt cerebrum by two-way ANOVA and post-hoc testing (P < 0.001) (Fig. 1D).While grt/grt mice have a defect in tyrosylprotein sulfotransferase 2 (Tpst2) gene, the cerebral volume reduction revealed in the present volumetric analysis may be rather involved in the hypothyroid status of grt/grt mice (Kobayashi et al. 2001), because similar cerebral hypoplasia is obtained by experimentallyinduced hypothyroid rats (Madeira et al. 1990). Thus, CT-or MRIbased volumetry can be screened changes in brain structures of smal...

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Responses of the Thyroid Gland to TSH and Other Thyroid Stimulators in the Growth-Retarded (grt) Mouse

Cited by 11 publications

References 25 publications

Impaired insulin secretion from the pancreatic islets of hypothyroidal growth-retarded mice

Impaired insulin secretion from the pancreatic islets of hypothyroidal growth-retarded mice

Testicular Development in Growth-Retarded Mice

Brain volumetry: A quantitative approach for detecting region‐specific structural abnormalities

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