Characterization of fetal urogenital sinus-induced prostatic hyperplasia in the mouse: time course, hormonal requirement, age dependency, and responsiveness of various adult organs to growth induction by fetal urogenital sinus tissues.
Mouse prostatic hyperplasia can be induced experimentally by the direct implantation of fetal urogenital sinus (UGS) or its mesenchyme (UGM) tissue in situ. This study characterized the time course, the requirement of sex steroids, and the optimal ages of donor and host tissues necessary to induce the maximal overgrowth of the adult mouse prostate gland in this model system. To test the potential uses of these fetal inductors as general growth-promoting substances for other adult organs, we have also tested directly the activity of fetal UGS in several non-UGS-derived adult organs. These results were compared with the growth-promoting effect achieved by fetal UGM in order to gain further insight into the relative contribution of UGS/UGM in the overall growth responses. Peak DNA synthesis in the implanted prostate occurred at three time periods-Days 4, 7-16, and 35. At Day 4, DNA synthesis may have reflected tissue repair following surgical trauma, but the DNA synthesis on Days 7-16 and 35 is attributable to growth of the chimeric (enlarged) prostate gland. Initiation and maintenance of hyperplasia required testicular androgens. Exogenous testosterone propionate (175 micrograms/day) did not induce additional prostatic overgrowth in intact, sexually mature hosts, but promoted additional overgrowth in immature and pubertal hosts. Exogenous estrogen (17 beta-estradiol dipropionate, 20 micrograms/day) inhibited fetal UGS-induced prostatic overgrowth by inhibiting the hypothalamic-pituitary-testicular axis. UGS derived from fetuses of Days 14, 16, or 18 of gestation had similar growth-inductive capability in intact adult hosts, but this capability was restricted soon after birth.(ABSTRACT TRUNCATED AT 250 WORDS)
Chung
L W
LW
Pharmacology/School of Pharmacy, University of Colorado, Boulder 80309-0297.
Auble
K
K
D000375:Aging; D000818:Animals; D004958:Estradiol / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009928:Organ Specificity; D011467:Prostate / Q000187:drug effects / Q000254:growth & development / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000209:etiology / Q000503:physiopathology*; D013739:Testosterone / Q000494:pharmacology; D014566:Urogenital System / Q000196:embryology / Q000637:transplantation*
D013739:Testosterone; D004958:Estradiol