Gesing Adam, Bartke Andrzej, Masternak Michal M, Lewiński Andrzej, Karbownik-Lewińska Małgorzata
Department of Oncological Endocrinology, Chair of Endocrinology and Metabolic Diseases, Medical University of Lodz, Lodz, Poland.
Thyroid Res. 2012 Aug 16;5(1):7. doi: 10.1186/1756-6614-5-7.
Altered somatotrophic signaling is among the most important potential mechanisms of extended longevity. Ames dwarf (df/df) mice are homozygous for mutation at the Prop-1 gene, leading to a lack of growth hormone (GH), prolactin and thyroid stimulating hormone (TSH). Mice homozygous for targeted disruption of the growth hormone receptor/growth hormone binding protein gene are known as GH receptor knockout (GHRKO) mice or "Laron dwarf". Both, df/df and GHRKO mice, are characterized by reduced body size, low plasma insulin and insulin-like growth factor-I (IGF-I), remarkably extended longevity, and severe (in df/df mice) or mild (in GHRKO mice) thyroid hypofunction. Recently, by crossing df/df and GHRKO mice, double-mutant Ames dwarf/GHRKO (df/KO) mice were created. Interestingly, these mice are smaller than Ames dwarfs or GHRKOs, and also have reduced insulin and IGF-I levels. The aim of the study was to investigate if and to what extent certain thyroid morphological parameters, such as inner follicular surface area, inner follicular perimeter, as well as the follicular epithelium thickness are changed in the examined dwarf mice.
This quantification was performed in thyroids collected from df/df, GHRKO and df/KO female mice, at approximately 5-6 months of age. We used a computerized plotting programme that combines a live microscopic image of the slide with an operator-generated overlay.
Inner follicular surface area and inner follicular perimeter were decreased in all examined kinds of dwarf mice as compared to normal animals. Furthermore, decreases in these two parameters were more pronounced in df/df and df/KO than in GHRKO mice. Concerning the follicular epithelium thickness, only a tendency towards decrease of this parameter was found in all three kinds of dwarf mice.
Parameters characterizing thyroid follicle size are decreased in all three examined models of dwarf mice, which may explain decreased thyroid hormone levels in both basal mutants (Ames dwarfs and GHRKOs). df/df mutation seems to predominate over GHRKO genetic intervention concerning their effects on thyroid growth. Beside TSH, also GH signaling seems to constitute a crucial element in the regulation of thyroid growth and, possibly, function.
生长激素信号改变是延长寿命最重要的潜在机制之一。艾姆斯侏儒（df/df）小鼠是Prop-1基因发生纯合突变的小鼠，导致缺乏生长激素（GH）、催乳素和促甲状腺激素（TSH）。生长激素受体/生长激素结合蛋白基因靶向敲除的纯合小鼠被称为生长激素受体敲除（GHRKO）小鼠或“拉龙侏儒”小鼠。df/df和GHRKO小鼠均具有体型减小、血浆胰岛素和胰岛素样生长因子-I（IGF-I）水平低、寿命显著延长以及严重（df/df小鼠）或轻度（GHRKO小鼠）甲状腺功能减退的特征。最近，通过将df/df和GHRKO小鼠杂交，培育出了双突变艾姆斯侏儒/GHRKO（df/KO）小鼠。有趣的是，这些小鼠比艾姆斯侏儒或GHRKO小鼠体型更小，胰岛素和IGF-I水平也更低。本研究的目的是调查在受试侏儒小鼠中，某些甲状腺形态学参数，如滤泡内表面积、滤泡内周长以及滤泡上皮厚度是否发生改变，以及改变的程度如何。
对约5 - 6月龄的df/df、GHRKO和df/KO雌性小鼠的甲状腺进行定量分析。我们使用了一个计算机绘图程序，该程序将载玻片的实时显微镜图像与操作员生成的叠加图相结合。
与正常动物相比，所有受试侏儒小鼠的滤泡内表面积和滤泡内周长均减小。此外，这两个参数在df/df和df/KO小鼠中的降低比在GHRKO小鼠中更明显。关于滤泡上皮厚度，在所有三种侏儒小鼠中仅发现该参数有降低的趋势。
在所有三种受试侏儒小鼠模型中，表征甲状腺滤泡大小的参数均降低，这可能解释了两种基础突变体（艾姆斯侏儒和GHRKO）甲状腺激素水平降低（的原因）。就对甲状腺生长的影响而言，df/df突变似乎比GHRKO基因干预更具主导性。除了TSH外，GH信号似乎也是调节甲状腺生长以及可能还有甲状腺功能的关键因素。
