TSH compensates thyroid-specific IGF-I receptor knockout and causes papillary thyroid hyperplasia.
TSH compensates thyroid-specific IGF-I receptor knockout and causes papillary thyroid hyperplasia.
复制标题
TSH 补偿甲状腺特异性 IGF-I 受体敲除并导致甲状腺乳头状增生。
作者：
Kathrin Müller;D. Führer;J. Mittag;N. Klöting;M. Blüher;R. Weiss;M. Many;K. Schmid;K. Krohn
虽然TSH刺激甲状腺生理学的各个方面，但IGF-I信号通过含有酪氨酸激酶的跨膜受体对TSH作用表现出容许性影响。为了更好地了解IGF-I受体在体内甲状腺中的重要性，我们在小鼠中用Tg启动子驱动的Cre-lox系统灭活了Igf1r。我们研究了甲状腺野生型、Igf1r（+/-）和Igf1r（-/-）基因型的雄性和雌性小鼠。靶向Igf1r失活确实短暂降低了杂合子和纯合子小鼠的甲状腺激素水平，并显著增加了TSH水平，而不影响甲状腺重量。Igf1r失活的甲状腺组织的组织学分析显示增生和异质性滤泡结构。从4月龄开始，我们检测了杂合子和纯合子小鼠的乳头状甲状腺结构。我们还注意到，与野生型小鼠相比，Igf1r基因座纯合甲状腺无效突变的雄性小鼠体重增加。在Igf1r（+/-）和Igf1r（-/-）小鼠中，检测到甲状腺过氧化物酶的mRNA和蛋白质减少，IGF-II受体的mRNA和蛋白质增加，但胰岛素受体、TSH受体和钠碘同向转运体的mRNA无显著变化。我们的研究结果表明，TSH的强烈增加有益于甲状腺乳头状增生，并完全补偿了甲状腺激素水平上IGF-I受体信号的丢失，而甲状腺重量没有显着增加。这可能表明IGF-I受体信号对甲状腺激素合成不太重要，但维持体内平衡和正常的甲状腺形态发生。
Although TSH stimulates all aspects of thyroid physiology IGF-I signaling through a tyrosine kinase-containing transmembrane receptor exhibits a permissive impact on TSH action. To better understand the importance of the IGF-I receptor in the thyroid in vivo, we inactivated the Igf1r with a Tg promoter-driven Cre-lox system in mice. We studied male and female mice with thyroidal wild-type, Igf1r(+/-), and Igf1r(-/-) genotypes. Targeted Igf1r inactivation did transiently reduce thyroid hormone levels and significantly increased TSH levels in both heterozygous and homozygous mice without affecting thyroid weight. Histological analysis of thyroid tissue with Igf1r inactivation revealed hyperplasia and heterogeneous follicle structure. From 4 months of age, we detected papillary thyroid architecture in heterozygous and homozygous mice. We also noted increased body weight of male mice with a homozygous thyroidal null mutation in the Igf1r locus, compared with wild-type mice, respectively. A decrease of mRNA and protein for thyroid peroxidase and increased mRNA and protein for IGF-II receptor but no significant mRNA changes for the insulin receptor, the TSH receptor, and the sodium-iodide-symporter in both Igf1r(+/-) and Igf1r(-/-) mice were detected. Our results suggest that the strong increase of TSH benefits papillary thyroid hyperplasia and completely compensates the loss of IGF-I receptor signaling at the level of thyroid hormones without significant increase in thyroid weight. This could indicate that the IGF-I receptor signaling is less essential for thyroid hormone synthesis but maintains homeostasis and normal thyroid morphogenesis.
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体型大鼠的垂体甲状腺设定点和促甲状腺素受体表达。
影响因子：
4.8
作者：
Moeller,LarsC;Alonso,Manuela;Liao,Xiaohui;Broach,Vance;Dumitrescu,Alexandra;VanSande,Jacqueline;Montanelli,Lucia;Skjei,Stephen;Goodwin,Charles;Grasberger,Helmut;Refetoff,Samuel;Weiss,RoyE
通讯作者：
Weiss,RoyE
DOI：
10.1016/j.bbrc.2009.02.035
发表时间：
2009-04-03
影响因子：
3.1
作者：
Arufe, Maria C.;Lu, Min;Lin, Reigh-Yi
通讯作者：
Lin, Reigh-Yi
人类甲状腺组织中胰岛素样生长因子受体的表征。
DOI：
--
发表时间：
1992
期刊：
Receptor
影响因子：
--
作者：
Cissewski,K;Wolf,M;Moses,AC
通讯作者：
Moses,AC
影响因子：
4.1
作者：
He, Jianing;Rosen, Clifford J.;Kream, Barbara E.
通讯作者：
Kream, Barbara E.