The vasopressin V1b receptor critically regulates hypothalamic-pituitary-adrenal aids activity under both stress and resting conditions
The vasopressin V1b receptor critically regulates hypothalamic-pituitary-adrenal aids activity under both stress and resting conditions
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DOI：
10.1172/jci200419656
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发表时间：
2004-01-01
影响因子：
15.9
通讯作者：
Tsujimoto, G
中科院分区：
文献类型：
--
作者：
Tanoue, A;Ito, S;Tsujimoto, G
神经垂体肽[Arg（8）]-加压素（AVP）通过三种不同的受体亚型V1a、V1b和V2发挥主要的生理作用。在这三种亚型中，加压素V1b受体特异性表达于垂体促肾上腺皮质激素细胞，并介导加压素对ACTH释放的刺激作用。为了研究V1b受体亚型在体内的功能作用，使用基因靶向来创建缺乏V1b受体基因（V1bR（-/-））的小鼠模型。在静息状态下，V1bR（-/-）小鼠的ACTH和皮质酮循环浓度低于WT小鼠（V1bR（+/+））。在V1bR（-/-）小鼠中，对外源性施用AVP的循环ACTH水平的正常增加受到损害，而V1bR（-/-）小鼠中促肾上腺皮质激素释放肽刺激的ACTH释放与V1bR（+/+）小鼠中的无显著差异。AVP诱导的V1bR（-/-）小鼠原代培养垂体细胞ACTH释放也被减弱。此外，在V1bR（-/-）小鼠中，强迫游泳应激后ACTH的增加被显著抑制。我们的研究结果清楚地表明，V1b受体在调节下丘脑-垂体-肾上腺轴活动中起着至关重要的作用。它通过维持ACTH和皮质酮水平来做到这一点，不仅在压力下，而且在基础条件下。
The neurohypophyseal peptide [Arg(8)]-vasopressin (AVP) exerts major physiological actions through three distinct receptor isoforms designated V1a, V1b, and V2. Among these three subtypes, the vasopressin V1b receptor is specifically expressed in pituitary corticotrophs and mediates the stimulatory effect of vasopressin on ACTH release. To investigate the functional roles of V1b receptor subtypes in vivo, gene targeting was used to create a mouse model lacking the V1b receptor gene (V1bR(-/-)). Under resting conditions, circulating concentrations of ACTH and corticosterone were lower in V1bR(-/-) mice compared with WT mice (V1bR(+/+)). The normal increase in circulating ACTH levels in response to exogenous administration of AVP was impaired in V1bR(-/-) mice, while corticotropin-releasing hormone-stimulated ACTH release in the V1bR(-/-) mice was not significantly different from that in the V1bR(+/+) mice. AVP-induced ACTH release from primary cultured pituitary cells in V1bR(-/-) mice was also blunted. Furthermore, the increase in ACTH after a forced swim stress was significantly suppressed in V1bR(-/-) mice. Our results clearly demonstrate that the V1b receptor plays a crucial role in regulating hypothalamic-pituitary-adrenal axis activity. It does this by maintaining ACTH and corticosterone levels, not only under stress but also under basal conditions.