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To study the role of epithelial-mesenchymal interactions in myometrial development, uteri from neonatal Balb/c mice 1 to 60 days postpartum were utilized. Intact (untrypsinized) uteri, trypsinized but unseparated uteri, homotypic uterine tissue recombinants (separated-recombined), or uterine mesenchyme alone were grafted beneath the renal capsule of syngeneic female hosts and grown for 1 mo. Uterine mesenchyme from 1-day mice grafted alone produced small amounts of smooth muscle, most of which was associated with vasculature, whereas uterine mesenchyme from older donors possessing a rudimentary myometrium at the time of grafting formed intermediate amounts of myometrium (actin-positive smooth muscle bundles). In contrast, all specimens containing epithelium (intact, trypsinized, and separated-recombined) developed large amounts of myometrium. Uterine epithelia from neonatal through adult stages were equally effective in permissively inducing myometrial development in 1-day uterine mesenchyme. From these data, it is apparent that uterine epithelium plays an important promotional role in the differentiation and possibly the spatial organization of the myometrium.

We have examined tissue recombinants composed of wild-type (rat or mouse) urogenital sinus mesenchyme plus adult testicular feminized (Tfm/y) bladder epithelium for the autoradiographic localization of androgen binding. In the presence of androgens, wild-type mesenchyme reprogrammed the androgen-insensitive bladder epithelium to undergo prostatic morphogenesis. Steroid autoradiography of [3H] dihydrotestosterone or [3H] methyltrienolone binding in these recombinants, however, showed that the ligands were specifically bound only in the nuclei of stromal cells, indicating that the effects of androgens on prostatic morphogenesis are mediated by the mesenchyme. Furthermore, autoradiograms prepared from recombinants that were exposed to [3H] thymidine showed that the generation of prostatic form required a specific, androgen-induced proliferation in the androgen-insensitive bladder epithelium. The significance of these data in relation to epithelial-stromal interactions occurring during prostate development is discussed.