Yamashita A, Hayashi N, Sugimura Y, Cunha G R, Kawamura J
Department of Urology, Mie University, School of Medicine, Mieken, Japan.
Prostate. 1996 Jul;29(1):1-14. doi: 10.1002/(SICI)1097-0045(199607)29:1<1::AID-PROS1>3.0.CO;2-K.
The effects of various means of interfering with androgen action on rat coagulating gland, ventral prostate, lateral type 1 prostate, lateral type 2 prostate, and dorsal prostate were examined morphologically and quantitatively by assessing DNA content, wet weight, protein content, and zinc concentrations. Adult male Sprague-Dawley rats were subjected to 2 weeks of interfering with androgen action by treatment with Leuprolelin (a luteinizing hormone-releasing hormone analog), Finasteride (a 5 alpha-reductase inhibitor), or diethylstilbestrol (DES), or by physical castration. For all prostatic lobes, inhibition of 5 alpha-reductase elicited the smallest reduction in prostatic wet weight, DNA and protein contents, and zinc concentration. The most profound reductions in all parameters were elicited by castration. Treatments with DES and Leuprolelin gave intermediate effects with DES being the more effective in reducing all parameters in all prostatic lobes. Morphological changes elicited by all forms of androgen blockade were reduction of epithelial height, relative increase of connective tissue, reduction in ductal diameter, length, and number. The order of effectiveness of the various treatments on morphological features was as described above. While all forms of androgen blockade elicited similar effects throughout the prostate, differences in response to all forms of interference with androgen action were observed in different lobes of the prostate with regard to wet weight, DNA and protein contents, and zinc concentration as well as morphological effects. Regressive changes at the morphological level were particularly striking in the coagulating gland and ventral prostate, and indistinct in the lateral type 2 prostate. Prostatic zinc concentration in both normal and androgen-deprived rats was the highest in the lateral type 2 prostate and was reduced by interfering with androgen action to the greatest extent in the dorsolateral prostate (lateral type 1 and type 2, and dorsal prostate). The distribution of zinc correlated with the expression of metallothionein, which was detected by immunocytochemistry only in the lateral type 2 prostate of both normal and androgen deprived rats. Intraprostatic heterogeneity of zinc and metallothionein expression emphasizes interlobar differences in biological function within the rat prostate. The mechanism of development of regional heterogeneity within the prostate may shed light on the pathogenesis of prostatic proliferative diseases (prostatic hyperplasia and prostatic cancer) that initially owe their development to focal changes within large cell populations.
通过评估DNA含量、湿重、蛋白质含量和锌浓度，从形态学和定量角度研究了多种干扰雄激素作用的方法对大鼠凝固腺、腹侧前列腺、外侧1型前列腺、外侧2型前列腺和背侧前列腺的影响。成年雄性Sprague-Dawley大鼠接受为期2周的雄激素作用干扰，方法包括使用亮丙瑞林（一种促黄体生成素释放激素类似物）、非那雄胺（一种5α-还原酶抑制剂）或己烯雌酚（DES）进行治疗，或进行物理去势。对于所有前列腺叶，抑制5α-还原酶引起的前列腺湿重、DNA和蛋白质含量以及锌浓度的降低最小。去势引起所有参数最显著的降低。DES和亮丙瑞林治疗产生中等效果，其中DES在降低所有前列腺叶的所有参数方面更有效。所有形式的雄激素阻断引起的形态学变化包括上皮高度降低、结缔组织相对增加、导管直径、长度和数量减少。各种治疗对形态学特征的有效性顺序如上所述。虽然所有形式的雄激素阻断在整个前列腺中引起相似的效应，但在前列腺的不同叶中，在湿重、DNA和蛋白质含量、锌浓度以及形态学效应方面，观察到对所有形式的雄激素作用干扰的反应存在差异。形态学水平的退行性变化在凝固腺和腹侧前列腺中尤为明显，而在外侧2型前列腺中不明显。正常和雄激素缺乏大鼠的前列腺锌浓度在外侧2型前列腺中最高，并且通过干扰雄激素作用，在背外侧前列腺（外侧1型和2型以及背侧前列腺）中降低程度最大。锌的分布与金属硫蛋白的表达相关，仅在正常和雄激素缺乏大鼠的外侧2型前列腺中通过免疫细胞化学检测到金属硫蛋白。前列腺内锌和金属硫蛋白表达的异质性强调了大鼠前列腺内叶间生物学功能的差异。前列腺内区域异质性的发展机制可能有助于揭示前列腺增生性疾病（前列腺增生和前列腺癌）的发病机制，这些疾病最初的发展归因于大细胞群体内的局灶性变化。
