Permissive and instructive induction of adult rodent prostatic epithelium by heterotypic urogenital sinus mesenchyme

Abstract

Adult rodent (rat and mouse) prostatic ducts (PR) were recombined heterospecifically with fetal urogenital sinus mesenchyme (UGM) (mouse UGM plus rat PR or rat UGM plus mouse PR), and the resultant tissue recombinants were grafted under the renal capsule of male athymic mice. For recombination with mouse UGM the ductal tips of each of the 4 rat prostatic lobes [ventral (VP), lateral type 1 (L1), lateral type 2 (L2), and dorsal prostate (DP)] were used. For recombination with rat UGM the ductal tips of each of the 2 mouse prostatic lobes [ventral (VP) and dorso-lateral prostate (DLP)] were used. After 1 month of growth in vivo, the DNA content of UGM+PR recombinants increased substantially (6.1- to 76.8-fold increase) over the combined DNA content of the isolated UGM and PR prior to grafting. Immunocytochemical, polyacrylamide gel electrophoretic and Western blot analyses demonstrated that irrespective of the initial source of the adult prostatic duct, the epithelium of UGM + PR recombinants continued to express its normal lobe-specific secretory proteins as well as secretory proteins specific to other prostatic lobes. For example, rat ventral and lateral type 2 prostate do not normally express DP-1, a rat dorsal-prostatic-specific protein, but after recombination with mouse UGM the induced prostatic epithelium expressed DP-1 as well as C3, a rat ventral-prostatic-specific protein. Sensitive reverse transcriptase-polymerase chain reaction techniques (RT-PCR) verified the expression of mRNA for C3 and DP-1 in such tissue recombinants. Analogous results were obtained for UGM + PR tissue recombinants constructed with prostatic ductal tips from rat L1, L2 and DP and mouse VP and DLP. These findings demonstrate that adult rodent prostatic epithelium retains a responsiveness to its connective tissue environment, and that fetal UGM can permissively induce prostatic ductal growth and morphogenesis while instructively inducing the expression of a new spectrum of prostatic secretory proteins.