2018 Volume 37 Issue 3 Pages 109-116
Objective：The purpose of this study was to examine the effect of chronic stress on the secretion of salivary epidermal growth factor (EGF).
Material and methods：A mouse receiving long-term phenylephrine (PHE), an α1-adrenergic receptor agonist, was used as a model to simulate chronic stress. Male ICR mice, at 12 weeks of age, were divided into 2 groups：a PHE group and a control (CTL) group. For the PHE group, PHE (5mg/kg) was injected intramuscularly twice a day for 5 days. Control mice received equivalent volume injections of saline alone. The pilocarpine-stimulated whole saliva was collected for 20 min, and then the submandibular gland (SMG) was removed. The salivary EGF concentration, and levels of EGF and EGF mRNA in the SMG extracts were determined. Immunohistochemical staining against EGF and pro-EGF in the SMG were observed. In the dispersed SMG cells, the EGF concentration stimulated by phorbol 12-myristate 13-acetate (PMA), an activator of PKC, was determined.
Results：The salivary EGF concentration was significantly lower in the PHE group than in the CTL group (p < 0.05). Concomitantly, the levels of EGF in the SMG extract were significantly lower in the PHE group than in the CTL group (p < 0.05), although there was no significant difference between the groups in the EGF mRNA levels. Immunohistochemistry revealed a reduction in the size of the EGF-immuno-reactive granular convoluted tubule (GCT) in the PHE group compared with the CTL group, suggesting that the GCT became atrophic or that depletion of cellular stores of mature EGF-containing secretory granules occurred. Similarly, the pro-EGF-immunereactive GCT was also reduced in the PHE group compared with the CTL group. Additionally, in the PHE group, EGF-immunereactive was weak in the secretory granule compare with that in the basolateral cytoplasm, suggesting that posttranslational processing from a precursor to active EGF via pro-EGF was impeded. In the dispersed SMG cells, although the EGF concentration was increased upon stimulation with PMA in the PHE group, there was no significant difference between the PHE and CTL.
Conclusion：The present results suggest that the salivary EGF was decreased by chronic stress due to the impairment of posttranslational processing and inhibition of intracellular signal transduction.
