Expression of cAMP response element-binding protein in the duct system of the mouse submandibular gland

The submandibular gland (SMG) of mice shows a marked sexual dimorphism in which a duct portion called the granular convoluted tubule (GCT) is developed preferentially in males during puberty. The administration of testosterone to female mice causes the conversion of striated duct (SD) cells into GCT cells, but the underlying molecular mechanisms are unclear. Cyclic AMP response element-binding protein (CREB) is a transcription factor functioning downstream of a variety of signal transduction pathways. In the present study, we examined the expression, activation and cellular localization of CREB in the mouse SMG using Western blotting and immunohistochemistry. Both total CREB (t-CREB) and phosphorylated CREB (p-CREB) were significantly more abundant in the female than in the male gland and were localized to the nuclei of intercalated duct cells and a subpopulation of SD cells. In contrast, the GCT cells in males were negative for t- and p-CREB. The levels of CREB in the SMG were increased by castration in males and decreased by repeated administration of testosterone to females or castrated males. From 3 h after a single administration of testosterone to females, many SD cells temporarily gained nuclear immunoreactivity for both t- and p-CREB, which was lost as the cells were converted to GCT cells by 24 h. These results suggest the involvement of CREB in the androgen-dependent differentiation of the duct system in the mouse SMG.