Long-Term corticosterone treatment induced lobe-specific pathology in mouse prostate

Ulla Simanainen, Anita Lampinen, Holger Henneicke, Tara C. Brennan, Uta Heinevetter, D. Tim Harwood, Keely McNamara, Markus Herrmann, Markus J. Seibel, David J. Handelsman, Hong Zhou

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

BACKGROUND Glucocorticoids influence prostate development and pathology, yet the underlying mechanisms including possible direct glucocorticoid effect on the prostate are not well characterized. METHODS We evaluated the expression of the glucocorticoid receptor (GR) together with the effects of supraphysiological glucocorticoid (corticosterone) on mouse prostate morphology and epithelial proliferation. Mature male mice were treated by weekly subdermal implantation of depot pellets containing either 1.5 mg corticosterone or placebo providing steady-state release for 4 weeks. RESULTS Corticosterone treatment significantly increased dorsolateral and anterior prostate weights as well as prostate epithelial cell proliferation while epithelial apoptosis remained low upon corticosterone treatment. Histological analysis of the anterior lobe demonstrated abnormal, highly disorganized luminal epithelium with frequent formation of bridge-like structures lined by continuous layer of basal cells not observed following placebo treatment. Molecular analysis revealed corticosterone-induced increase in expression of stromal growth factor Fgf10 which, together with prominent stromal GR expression, suggest that glucocorticoid modify stromal-to-epithelial signaling in the mouse prostate. The mitogenic effects were prostate specific and not mediated by systemic effects on testosterone production suggesting that corticosterone effects were primarily mediated via prostate GR expression. CONCLUSION These data demonstrate that murine prostate is significantly and directly influenced by corticosterone treatment via aberrant stromal-to-epithelial growth factor signaling. Prostate 71:289-297, 2011. © 2010 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)289-297
Number of pages9
JournalProstate
Volume71
Issue number3
DOIs
Publication statusPublished - 2011 Feb 15

Keywords

  • corticosterone
  • glucocorticoid receptor
  • mouse
  • prostate
  • prostate pathology

ASJC Scopus subject areas

  • Oncology
  • Urology

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