Shabsigh A, Chang D T, Heitjan D F, Kiss A, Olsson C A, Puchner P J, Buttyan R
Department of Urology, The College of Physicians and Surgeons of Columbia University, New York, New York, USA.
Prostate. 1998 Aug 1;36(3):201-6. doi: 10.1002/(sici)1097-0045(19980801)36:3<201::aid-pros9>3.0.co;2-j.
Androgenic steroids regulate the development and size of the mammalian prostate gland. The mechanism(s) for this growth control might involve a direct effect on prostate cell proliferation and survival as well as more complex effects on the tissue environment supporting nourishment and oxygenation. In this study, we evaluated an animal model of androgen action on the prostate, the rat ventral prostate gland, to determine whether acute androgen withdrawal, by means of castration, might alter the primary blood flow to the prostate gland and for the effects of castration on prostatic endothelial cell viability.
Groups of rats studied included intact control males, males that had been surgically castrated, or males that received a sham-surgical castration. Relative blood flow (RBF) to the rat ventral prostate glands and rat bladders were measured at 18 and 24 hr after castration or sham castration using a fluorescent microsphere infusion technique. Thin sections from fixed and embedded rat ventral prostate glands obtained from unoperated or 12-hr castrated rats were analyzed by the TUNEL immunostaining technique to microscopically identify and quantify apoptotic epithelial, stromal, and endothelial cells.
RBF to the rat ventral prostate was reduced by 38%, at 18 hr after castration when compared with intact or sham-operated rats and by 45% at 24 hr after castration (P=0.038 unoperated/0.025 sham operated). In contrast, RBF to the bladder was not significantly different between any of the groups in the 24-hr castrate experiment. TUNEL staining analysis of ventral prostate tissues obtained from 12-hr castrated rats showed only rare TUNEL-positive epithelial cells similar to the control tissue but significantly increased TUNEL labeling for endothelial and other ventral prostate stromal cells.
Castration resulted in a rapid and significant reduction of blood flow to the mature rat ventral prostate gland that was not seen in the bladder. This reduction precedes the appearance of apoptosis in the epithelial cells of the tissue but more coincided with the appearance of TUNEL-positive prostate vascular endothelial and stromal cells, suggesting that androgens support the survival of cells in the vascular and stromal compartment of the rat prostate as well as in the prostatic epithelium. These preliminary data support the concept that androgen action on the prostate might involve primary regulation of prostate blood flow and prostate vascular cell vitality.
雄激素类固醇调节哺乳动物前列腺的发育和大小。这种生长控制机制可能涉及对前列腺细胞增殖和存活的直接影响,以及对支持营养和氧合的组织环境的更复杂影响。在本研究中,我们评估了雄激素对前列腺作用的动物模型——大鼠腹侧前列腺,以确定通过去势实现的急性雄激素撤除是否可能改变前列腺的主要血流,以及去势对前列腺内皮细胞活力的影响。
所研究的大鼠组包括完整对照雄性大鼠、接受手术去势的雄性大鼠或接受假手术去势的雄性大鼠。使用荧光微球灌注技术在去势或假去势后18小时和24小时测量大鼠腹侧前列腺和膀胱的相对血流(RBF)。通过TUNEL免疫染色技术分析从未手术或去势12小时的大鼠获得的固定和包埋的大鼠腹侧前列腺的薄切片,以显微镜下鉴定和量化凋亡的上皮细胞、基质细胞和内皮细胞。
与完整或假手术大鼠相比,去势后18小时大鼠腹侧前列腺的RBF降低了38%,去势后24小时降低了45%(未手术组P = 0.038/假手术组P = 0.025)。相比之下,在24小时去势实验中,任何组之间膀胱的RBF均无显著差异。对去势12小时的大鼠腹侧前列腺组织进行的TUNEL染色分析显示,与对照组织相似,仅罕见的TUNEL阳性上皮细胞,但内皮细胞和其他腹侧前列腺基质细胞的TUNEL标记显著增加。
去势导致成熟大鼠腹侧前列腺的血流迅速且显著减少,而膀胱中未出现这种情况。这种减少先于组织上皮细胞凋亡的出现,但更与TUNEL阳性前列腺血管内皮细胞和基质细胞的出现一致,表明雄激素支持大鼠前列腺血管和基质区室以及前列腺上皮细胞的存活。这些初步数据支持了雄激素对前列腺的作用可能涉及前列腺血流和前列腺血管细胞活力的主要调节这一概念。