Article
Lab Invest 2000, 80:993–1006
Epithelial Defect in Prostates of Stat5a-Null Mice
This work was supported by the Academy of Finland, International Agency of Research on Cancer, Turku Postgraduate School, and the National Institutes of Health Grant RO1 DK52013 (to ).
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Marja T Nevalainen1, Tommi J Ahonen1,4, Hiroko Yamashita1, Varadaraj Chandrashekar3, Andrzej Bartke3, Philip M Grimley1, Gertraud W Robinson2, Lothar Hennighausen2 and Hallgeir Rui1
- 1Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, Maryland
- 2Laboratory of Genetics and Physiology, National Institutes of Diabetes and Kidney Diseases, National Institutes of Health, Bethesda, Maryland
- 3Department of Physiology, Southern Illinois University, Life Science II, Carbondale, Illinois
- 4Department of Anatomy, Institute of Biomedicine, University of Turku, Turku, Finland
Correspondence: Dr. H. Rui, Department of Pathology, Uniformed Services University of the Health Sciences School of Medicine, Bethesda, Maryland 20814. Fax: (301) 295-1640; E-mail: hrui@usuhs.mil
Received 28 December 1999.
Abstract
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.
