Male human populations that are at high risk for prostate cancer often have higher circulating testosterone levels that populations that are at lower risk for this disease. Circulating testosterone levels are particularly high in pregnant women of high risk populations compared with lower risk populations. Perinatal administration of considerable doses of diethylstilbestrol (DES) to male mice causes carcinomas and preneoplasia of the accessory sex glands, including the prostate. These data suggest that prenatal exposure to DES and androgens increases risk for prostate cancer development later in life. This proposal seeks to test this hypothesis. We will expose male rats in utero and/or neonatally to testosterone or DES at doses that are not teratogenic or toxic, as to be determined in preliminary studies. Subsequently, we will expose these rats to treatments that have been shown to induce prostate cancer in rats that were not exposed to exogenous hormones perinatally. We will then compare the incidence, multiplicity and latency of prostate carcinomas in the perinatally hormone exposed rats with these parameters in rats that were not exposed prenatally. We will use three models of prostate cancer induction that differ in their mechanism of action: (1) chronic testosterone administration, (2) a single injection with N-methyl-N-nitrosourea followed by chronic testosterone administration, and (3) chronic administration of estradiol-17beta and testosterone. In addition, we will determine the effects of perinatal androgen and DES exposure on circulating testosterone and on androgen and estrogen sensitivity of the male accessory sex glands, including the prostate.
| Bosland, M C (2000) The role of steroid hormones in prostate carcinogenesis. J Natl Cancer Inst Monogr :39-66 |
| Condon, M S; Bosland, M C (1999) The role of stromal cells in prostate cancer development and progression. In Vivo 13:61-5 |
| Bosland, M C (1996) Hormonal factors in carcinogenesis of the prostate and testis in humans and in animal models. Prog Clin Biol Res 394:309-52 |
