Acquisition of androgen-mediated expression of mouse vas deferens protein (MVDP) gene in cultured epithelial cells and in vas deferens during postnatal development

We used cultured vas deferens epithelial cells (VDECs) as a model system to determine the conditions that allow mouse vas deferens protein (MVDP) gene expression and acquisition of androgen responsiveness. On the basis of Nor thern blot analysis, the mvdp gene is constitutively expressed at very low levels in prepubertal VDECs grown on collagen-coated plastic or on micropor ous membrane inserts. In the presence of dihydrotestosterone (DHT), mvdp me ssenger RNA levels dramatically increased in cells cultured on microporous membrane inserts and stayed unchanged in cells grown on matrix-coated plast ic. Epithelial cells derived from fetal vas deferens were able to synthesiz e MVDP in response to DHT, and the presence of fetal mesenchymal cells did not influence MVDP production. Providing the cells with a culture procedure that permits access to the basolateral membranes and caters to the polarit y requirements of the cell is a prerequisite for androgen induction of MVDP gene expression. The results also point to a role for epidermal growth fac tor, insulin, and tyrosine kinase activity in mediating the action of andro gen on mvdp gene expression. In vivo studies show that the first expression of the mvdp gene between 5 and 7 days postpartum is not associated with ma jor structural changes in the epithelium. The acquisition of a mature pheno type by epithelial and peritubular contractile cells, between 10 and 20 day s, correlates with androgen dependency of the mvdp gene. We propose that ce ll differentiation and polarization on a matrix-coated microporous membrane reproduces some of the events that are necessary for acquisition of androg enic responsiveness of the mvdp gene during postnatal development.