The signal-transduction mechanisms of the cell proliferation and differentiation in the submandibular gland

在啮齿类动物的下颌下腺（SMG）中，腺泡细胞在出生后早期的增殖和分化依赖于β肾上腺素能自主神经系统，而腺管细胞在青春期向颗粒曲小管（GCT）细胞的分化依赖于雄激素。在本研究中，我们揭示了以下几点：1）免疫组化和反义抑制技术表明，在大鼠SMG中，无论是增殖期的腺泡细胞还是向GCT细胞分化的导管细胞，转录因子CREB都暂时存在于细胞核中，并在细胞增殖和分化中起重要作用; 2）产后3-4周，腺泡细胞停止增殖向分化转变时，位于腺泡中央的未成熟细胞在向成熟腺泡细胞分化前暂时表达25 kD的热休克蛋白（Hsp 25）; 3）垂体切除大鼠SMG中，单次给予β肾上腺素能激动剂异丙肾上腺素24 h后，蛋白酶抑制剂cystatinSmRNA的诱导作用明显低于对照组。给予一种垂体依赖性激素，即，睾酮、雌二醇、地塞米松和甲状腺素与异丙肾上腺素一起可显著恢复胱抑素S mRNA的表达。4）在小鼠SMG中，癌基因产物和转录因子JunD的表达定位于导管系统，并且在雌性腺体中比在雄性腺体中丰富得多。在出生后的发育和睾酮诱导的GCT细胞分化过程中，JunD在纹状管细胞核中的表达被暂时诱导，并随着它们向GCT细胞的分化而消失，这些结果表明啮齿动物SMG腺泡和导管成分的增殖和分化存在多个信号通路之间的交叉对话。

In the rodent submandibular glands (SMG), acinar cell proliferation and differentiation in the early postnatal weeks are dependent on the β adrenergic autonomic nervous system, whereas the differentiation of duct cells into granular convoluted tubule (GCT) cells in the puberty is dependent on androgens. In the present study, we have revealed the following things :1) In both the proliferating acinar cells and the duct cells undergoing differentiation into GCT cells in the rat SMG, the transcription factor CREB occurs temporalily in the nuclei and plays essential roles in the cell proliferation and differentiation as shown by mmunohistochemistry and the antisense inhibition technique.2) During 3-4 weeks postpartum, when the acinar cells stop proliferation and switch to differentiation, the immature cells located in the center of the acini temporarily express the 25 kD heat shock protein (Hsp25) before they differentiate into the mature acinar cells.3) In the SMG of hypophysectomized rat, the induction of the protease inhibitor cystatin S mRNA 24 h afer a single administration of the β 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 the cystatin S mRNA expression.4) In the SMG of mice, the expression of JunD, an oncogen product and transcription factor, is localized to the duct system and much more abundant in the female than in the male gland. During the postnatal development and the testosterone-induced GCT cell differentiation, JunD expression is temporarily induced in the nuclei of striated duct cells and disappeares as they differentiate into GCT cells.These results suggested the existence of cross-talks between multiple signaling pathways responsible for the proliferation and differentiation of acinar and duct components of the rodent SMG.