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The mechanism of androgen-dependent differentiation of the duct system in the submandibular gland

颌下腺导管系统雄激素依赖性分化机制

基本信息

批准号：
15590156
负责人：
ISEKI Shoichi
金额：
$ 2.3万
依托单位：
Kanazawa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

In regard to the differentiation of rodent submandibular glands (SMG), we have obtained the following results :1)In the mouse SMG, the expression of the transcription factor JunD is localized to the duct system and much more abundant in the female than in the male gland. During the postnatal development and testosterone-induced GCT cell differentiation, JunD expression is temporarily induced in the nuclei of striated duct cells and dispappeares as they differentiated into GCT cells (Reference 1).2)The expression and localization of menin, a nuclear protein that binds JunD, showed the same pattern in the mouse SMG as that of JunD, suggesting that JunD-menin complex is responsible for the duct differentiation.3)In the SMG of hypophysectomized rats, the induction of the protease inhibitor cystatin S by the b-adrenergic agonist isoproterenol is much less than that in the control. Administration of one of the pituitary-dependent hormones, i.e., testosterone, estradiol, dexamethasone and thyroxine, together with isoproterenol results in marked recovery of cystatin S expression (Reference 2).These results suggest the role of cross-talks between multiple signaling pathways, including that of androgens, in the differentiation of rodent SMG.4)We have cloned a novel animal lectin specifically expressed in the rat sublingual gland and named it STAMP (sublingual gland acinar membrane protein). SLAMP is localized to the membrane of ER-Golgi intermediate compartment (ERGIC), suggesting its role in the early secretory pathway of mucin glycoproteins.

关于啮齿类动物颌下腺(SMG)的分化，我们获得了以下结果：1)在小鼠SMG中，转录因子Jund的表达定位于导管系统，且雌性比雄性丰富。在出生后发育和睾酮诱导的GCT细胞分化过程中，Jund在纹状管细胞的细胞核中暂时诱导表达，并在分化为GCT细胞时消失(参考文献1)2)与Jund结合的核蛋白menin在小鼠SMG中的表达和定位显示出与Jund相同的模式，表明Jund-menin复合体参与了GCT细胞的分化。3)在垂体切除大鼠的SMG中，β-肾上腺素能激动剂异丙肾上腺素诱导的蛋白酶抑制剂cystatin S的诱导作用明显低于对照组。睾酮、雌二醇、地塞米松和甲状腺素是一种垂体依赖性激素，与异丙肾上腺素共同作用后，半胱氨酸氨基转移酶S的表达显著恢复(参考文献2)。这些结果表明包括雄激素在内的多条信号通路之间的相互作用在啮齿动物SMG分化中的作用。4)我们克隆了一种新的动物凝集素，该凝集素在大鼠舌下腺中特异表达，并命名为STAMP(舌下腺泡膜蛋白)。SLAMP定位于内质网高尔基体中间室(ERGIC)的膜上，提示其在粘蛋白糖蛋白的早期分泌途径中起作用。