Nevalainen M T, Ahonen T J, Yamashita H, Chandrashekar V, Bartke A, Grimley P M, Robinson G W, Hennighausen L, Rui H
Department of Pathology, Uniformed Services University of the Health Sciences, and National Institutes of Diabetes and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Lab Invest. 2000 Jul;80(7):993-1006. doi: 10.1038/labinvest.3780105.
The transcription factor Stat5a critically mediates prolactin (PRL)-induced mammary gland development and lactogenesis. PRL also stimulates growth and differentiation of prostate tissue. Specifically, hyperprolactinemia gives rise to prostate hyperplasia, and prostate size is reduced in PRL-deficient mice. We therefore investigated the importance of Stat5a for prostate development and function by examining Stat5a-null mice. The absence of Stat5a in mice was associated with a distinct prostate morphology characterized by an increased prevalence of local disorganization within acinar epithelium of ventral prostates. Affected acini were typically filled with desquamated, granular epithelial cells that had become embedded in dense, coagulated secretory material. These features were reminiscent of acinar cyst formation and degeneration frequently observed in human benign prostate hyperplasia, however, cystic changes in prostate acini of Stat5a-deficient mice were not associated with increased prostate size or morphologic hallmarks of epithelial hyperplasia. Instead, immunohistochemistry of the prostate-specific secretory marker, probasin, suggested that hypersecretory function of the epithelium could underlie local congestion and cyst formation in prostates of Stat5a-null mice. Serum testosterone and PRL levels were normal in Stat5a knockout mice, but prostate PRL receptor expression was reduced as determined by immunohistochemistry. Expression levels or activation states of other PRL signal transduction proteins, including Stat5b, Stat3, Stat1, ERK1, and ERK2 were not altered. The present study offers the first evidence for a direct role of Stat5a in the maintenance of normal tissue architecture and function of the mouse prostate.
转录因子Stat5a对催乳素（PRL）诱导的乳腺发育和泌乳起着关键的介导作用。PRL还能刺激前列腺组织的生长和分化。具体而言，高催乳素血症会导致前列腺增生，而在PRL缺乏的小鼠中前列腺体积会减小。因此，我们通过研究Stat5a基因敲除小鼠来探究Stat5a对前列腺发育和功能的重要性。小鼠中Stat5a的缺失与一种独特的前列腺形态有关，其特征是腹侧前列腺腺泡上皮内局部结构紊乱的发生率增加。受影响的腺泡通常充满了已脱落的、颗粒状的上皮细胞，这些细胞已嵌入致密的、凝固的分泌物质中。这些特征使人联想到在人类良性前列腺增生中经常观察到的腺泡囊肿形成和退化，然而，Stat5a基因敲除小鼠前列腺腺泡的囊性变化与前列腺体积增加或上皮增生的形态学特征无关。相反，前列腺特异性分泌标记物前列腺素的免疫组化表明，上皮的高分泌功能可能是Stat5a基因敲除小鼠前列腺局部充血和囊肿形成的基础。Stat5a基因敲除小鼠的血清睾酮和PRL水平正常，但通过免疫组化测定发现前列腺PRL受体表达降低。其他PRL信号转导蛋白，包括Stat5b、Stat3、Stat1、ERK1和ERK2的表达水平或激活状态没有改变。本研究首次提供了证据，证明Stat5a在维持小鼠前列腺正常组织结构和功能中起直接作用。
