EFFECTS OF ESTROGEN ON PROSTATE FUNCTION DURING AGING

在拟议的实验中要检验的假设是， 男性在胎儿期暴露的性腺类固醇水平 在确定正常功能和发病率方面发挥重要作用 前列腺和前列腺的病理以及生育能力 在雄性小鼠（Mus martiticus）的衰老过程中。 初步研究已经 结果显示，在哺乳期间血清雌二醇（E2）略微升高的雄性小鼠， 胎儿一生有前列腺增大者，前列腺数量最多 雄激素受体，和性行为的最高率， 成年 相反，暴露于高剂量（药理学）E2 对前列腺重量的影响正好相反， 雄激素受体 胎儿期雌激素暴露的影响 因此，对雄性附属生殖器官的影响具有剂量依赖性。 我们 实验程序涉及用一系列的 在怀孕的最后三分之一的E2剂量，和初步研究 已经完成，以确定增加血清E2的剂量， 相对于未处理雄性，雄性胎仔为50-500%。 我们还将 施用一定剂量的睾酮（T），其升高男性中的血清T 50%的胎儿，由于一个令人惊讶的初步发现， 成年后前列腺重量显著下降。 每只的雄性 产前检查治疗组将在青壮年、中年 以及性腺完整或阉割/肾上腺切除术后的老年 替代性腺类固醇，以控制任何潜在的影响， 产前治疗对性腺类固醇水平的影响 酶活性， 生育能力，睾丸和附睾中的精子数量， 前列腺和前列腺中的雌激素受体数量 考察 将通过以下方法评估这些器官的区域异质性： 进行形态计量分析结合原位杂交 雄激素和雌激素受体mRNA的组织化学（ISHH）;这些 研究将使用来自相同器官的切片。 除了审查 来自年轻成年人、中年人和老年男性的器官、组织也将被 在胎儿期收集用于形态测定和ISHH分析， 前列腺和前列腺的分化。

The hypothesis to be tested in the proposed experiments is that the levels of gonadal steroids to which males are exposed during fetal life play a major role in determining the normal functioning of, and incidence of pathology in, prostate and coagulating glands as well as fertility during aging in male mice (Mus domesticus). Preliminary studies have shown that male mice with slightly elevated serum estradiol (E2) during fetal life have enlarged prostates, the greatest number of prostatic androgen receptors, and the highest rates of sexual behavior in adulthood. In contrast, exposure to a high (pharmacological) dose of E2 during fetal life has exactly the opposite effect on prostate weight and androgen receptors. The effects of estrogen exposure during fetal life on male accessory reproductive organs is thus dose dependent. Our experimental procedure involves treating pregnant females with a range of doses of E2 during the last third of pregnancy, and preliminary studies have been completed to determine the doses which increase serum E2 in male fetuses from 50-500% relative to untreated males. We will also administer a dose of testosterone (T) which elevates serum T in male fetuses by 50%, due to a surprising preliminary finding that this leads to a marked decrease in prostate weight in adulthood. Males from each prenatal treatment group will be examined in young adulthood, middle age and old age when gonadally intact or after castration/ adrenalectomy and replacement of gonadal steroids to control for any potential effects of prenatal treatment on gonadal steroid levels. Enzyme activity, fertility, sperm numbers in testes and epididymides, and both androgen and estrogen receptor numbers in prostate and coagulating glands will be examined. Regional heterogeneity of these organs will be assessed by conducting morphometric analysis coupled with in situ hybridization histochemistry (ISHH) for androgen and estrogen receptor mRNA's; these studies will use sections from the same organs. In addition to examining organs from young adult, middle aged, and old males, tissue will also be collected for morphometric and ISHH analysis during the fetal period of differentiation of prostate and coagulating glands.