Disruption of neuromedin B receptor gene results in dysregulation of the pituitary-thyroid axis.
Disruption of neuromedin B receptor gene results in dysregulation of the pituitary-thyroid axis.
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DOI：
10.1677/jme.1.01892
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发表时间：
2006-02
影响因子：
3.5
通讯作者：
K. Oliveira;T. Ortiga-Carvalho;Adriana Cabanelas;M. A. L. Veiga;K. Aoki;Hiroko Ohki-Hamazaki;K. Wada;E. Wada;C. Pazos-Moura
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文献类型：
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作者：
K. Oliveira;T. Ortiga-Carvalho;Adriana Cabanelas;M. A. L. Veiga;K. Aoki;Hiroko Ohki-Hamazaki;K. Wada;E. Wada;C. Pazos-Moura
促甲状腺激素（TSH）的分泌水平由促甲状腺激素释放激素（TRH）和甲状腺激素的平衡决定。然而，神经介肽B（NB），一种蛙皮素样肽，高度集中在垂体，已被假定为TSH分泌的紧张性抑制剂。我们研究了缺乏NB受体（NBR-KO）的成年雄性小鼠及其野生型（WT）同窝仔的垂体-甲状腺轴。在基础状态下，NBR-KO小鼠的血清TSH略高于WT（18%，P< 0.05），垂体内TSH含量正常，α和β TSH mRNA水平无显著变化。NBR-KO小鼠血清甲状腺素正常，但血清三碘甲状腺原氨酸（T3）降低了24%（P< 0.01）。NBR-KO小鼠垂体催乳素mRNA表达无变化，但I型和II型脱碘酶mRNA表达分别降低53%和42%（P< 0.05），而TRH受体mRNA表达显著升高（78%，P< 0.05）。TRH在NBR-KO小鼠中的促甲状腺激素释放作用显著高于WT小鼠（分别为7.1倍和4.0倍），但是，WT小鼠在TRH后血清T3增加了27%（P< 0.05），而NBR-KO小鼠在TRH后血清T3没有变化。NBR-KO小鼠对外源性NB没有反应，而WT显示血清TSH降低30%。NB或其他蛙皮素相关肽和受体（胃泌素释放肽（GRP），GRP受体和蛙皮素受体亚型-3）的mRNA表达在NBR-KO小鼠的垂体中没有发现代偿性变化。因此，这些数据表明，NB受体途径在促甲状腺激素基因调控和功能中起重要作用，导致TSH释放特别是响应TRH而促进的状态，但可能是生物活性较低的TSH。因此，该研究突出了NB作为垂体-甲状腺轴功能和基因表达的生理调节剂的重要作用。
The level of thyrotropin (TSH) secretion is determined by the balance of TSH-releasing hormone (TRH) and thyroid hormones. However, neuromedin B (NB), a bombesin-like peptide, highly concentrated in the pituitary, has been postulated to be a tonic inhibitor of TSH secretion. We studied the pituitary-thyroid axis in adult male mice lacking NB receptor (NBR-KO) and their wild-type (WT) littermates. At basal state, NBR-KO mice presented serum TSH slightly higher than WT (18%, P< 0.05), normal intra-pituitary TSH content, and no significant changes in alpha and beta TSH mRNA levels. Serum thyroxine was normal but serum triiodothyronine (T3) was reduced by 24% (P< 0.01) in NBR-KO mice. Pituitaries of NBR-KO mice exhibited no alteration in prolactin mRNA expression but type I and II deiodinase mRNA levels were reduced by 53 and 42% respectively (P< 0.05), while TRH receptor mRNA levels were importantly increased (78%, P< 0.05). The TSH-releasing effect of TRH was significantly higher in NBR-KO than in WT mice (7.1-and 4.0-fold respectively), but, while WT mice presented a 27% increase in serum T3 (P< 0.05) after TRH, NBR-KO mice showed no change in serum T3 after TRH. NBR-KO mice did not respond to exogenous NB, while WT showed a 30% reduction in serum TSH. No compensatory changes in mRNA expression of NB or other bombesin-related peptides and receptors (gastrin-releasing peptide (GRP), GRP-receptor and bombesin receptor subtype-3) were found in the pituitary of NBR-KO mice. Therefore, the data suggest that NB receptor pathways are importantly involved in thyrotroph gene regulation and function, leading to a state where TSH release is facilitated especially in response to TRH, but probably with a less-bioactive TSH. Therefore, the study highlights the important role of NB as a physiological regulator of pituitary-thyroid axis function and gene expression.