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In the submandibular gland (SMG) of mice, a duct portion called the granular convoluted tubule (GCT) is developed preferentially in males with puberty. This sexual dimorphism is androgen-dependent, but the underlying molecular mechanisms are unclear. We have demonstrated that the expression of a transcription factor JunD is regulated in association with the androgen-induced differentiation of GCT cells from striated duct (SD) cells. Menin, a nuclear protein encoded by the MEN1 tumor-suppressor gene, is known to bind JunD, thereby inhibiting its activity. In the present study, we examined the expression of menin in the mouse SMG by use of Northern blotting, Western blotting, and immunohistochemistry. Immunoreactivity for menin was higher in the female than male gland, and localized to the nuclei of intercalated duct cells and a subpopulation of SD cells. In contrast, GCT cells in males appeared negative for menin. The levels of menin in the SMG were increased with castration in males and decreased by repeated administration of testosterone to females or to castrated males. After a single administration of testosterone to females, many SD cells newly gained nuclear menin, which was lost as the cells converted to GCT cells by 48 hrs. These patterns of the expression and localization of menin were quite similar to those of JunD. Furthermore, the coimmunoprecipitation analysis of the SMG homogenates indicated that menin binds JunD in vivo. The present study suggests that the JunD-menin complex plays significant roles in the androgen-dependent differentiation of the duct system in the mouse SMG.

Coexpression of Menin and JunD during the Duct Cell Differentiation in Mouse Submandibular Gland