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

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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.