The role of cyclic AMP response element-binding protein in the differentiation of granular convoluted tubule cells in the rat submandibular gland

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During postnatal development of the submandibular glands of rodents, the differentiation of granular convoluted tubule (GCT) cells from striated duct cells is known to be androgen-dependent, but its molecular mechanism is unknown. We administered testosterone to 3W-old rats and examined the expression and localization of epidermal growth factor (EGF), the marker of GCT cells, as well as those of the transcription factor, cyclic AMP response element-binding protein (CREB) in the submandibular gland. One to 4 days after the administration of testosterone, increase in the levels of mRNA of both EGF and CREB was detected in the gland by Northern blot analysis. With immunoprecipitation, increase in the amount of phosphorylated CREB was also observed. In situ hybridization and immunohistochemistry demonstrated that the cells at the distal end of the striated duct became positive for both CREB mRNA and nuclear CREB immunoreactivity. The CREB signals were no longer detected in the mature GCT cells that are positive for EGF mRNA and EGF immunoreactivity. When the gland from 3 W-rats was subjected to the organ culture for 4 days in the presence of the antisense oligonucleiotide against CREB mRNA, the testosterone-induced increase of EGF mRNA was significantly inhibited. These results suggested that the signal transduction involving CREB is essential inthe postnatal development of GCT in the rat submandibular gland.
日本組織細胞化学会の論文