Prostate hyperplasia in a transgenic mouse with prostate-specific expression of prolactin
Prostate hyperplasia in a transgenic mouse with prostate-specific expression of prolactin
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DOI：
10.1210/en.2002-0187
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发表时间：
2003-06-01
期刊：
影响因子：
4.8
通讯作者：
Wennbo, H
中科院分区：
文献类型：
--
作者：
Kindblom, J;Dillner, K;Wennbo, H
催乳素（PRL）是已知对前列腺发挥营养作用的几种多肽因子之一。我们以前曾报道过一个显着的前列腺肿大并发慢性高催乳素血症和血清雄激素水平升高的PRL转基因小鼠（Mt-PRL）与无处不在的表达的转基因。为了解决在前列腺中的局部PRL作用的作用，使用前列腺特异性大鼠probasin（Pb）最小启动子来驱动大鼠PRL基因的表达，产生了新的转基因小鼠模型（Pb-PRL）。Pb-PRL转基因雄性动物的背外侧和腹侧前列腺叶明显增大，从10周龄开始，并随着年龄的增长而增加。转基因的表达仅限于前列腺，并从4周龄开始检测。在成年Pb-PRL动物的血清中可检测到低水平的转基因大鼠PRL。血清雄激素水平正常。Pb-PRL前列腺显示显著的间质增生、导管扩张和上皮异型增生的局灶性区域。前列腺组织细胞构成的定量分析表明，与对照组相比，Mt-PRL和Pb-PRL转基因前列腺的所有叶中的间质与上皮的比率显著增加。显微解剖显示，与Pb-PRL和对照组相比，Mt-PRL前列腺的背外侧和腹侧前列腺叶的导管形态发生增加。总之，这项研究表明，PRL的能力，以促进，直接或间接，导管形态发生在发展中的前列腺，并进一步诱导异常生长，主要是在成年腺体中的基质在设置正常的雄激素水平。
Prolactin (PRL) is one of several polypeptide factors known to exert trophic effects on the prostate. We have previously reported a dramatic prostate enlargement with concurrent chronic hyperprolactinemia and elevated serum androgen levels in a PRL transgenic mouse (Mt-PRL) with ubiquitous expression of the transgene. To address the role of local PRL action in the prostate, a new transgenic mouse model (Pb-PRL) was generated using the prostate-specific rat probasin (Pb) minimal promoter to drive expression of the rat PRL gene. Pb-PRL transgenic males developed a significant enlargement of both the dorsolateral and ventral prostate lobes evident from 10 wk of age and increasing with age. Expression of the transgene was restricted to the prostate and detected from 4 wk of age. Low levels of transgenic rat PRL were detectable in the serum of adult Pb-PRL animals. Serum androgen levels were normal. The Pb-PRL prostate displayed significant stromal hyperplasia, ductal dilation, and focal areas of epithelial dysplasia. Quantitative analysis of prostatic tissue cellularity demonstrated a marked increase in the stromal to epithelial ratio in all lobes of Mt-PRL and Pb-PRL transgenic prostates compared with controls. Microdissections demonstrated an increased ductal morphogenesis in dorsolateral and ventral prostate lobes of Mt-PRL prostate vs. Pb-PRL and controls. In conclusion, this study indicates the ability of PRL to promote, directly or indirectly, ductal morphogenesis in the developing prostate and further to induce abnormal growth primarily of the stroma in the adult gland in a setting of normal androgen levels.