title: Long-term corticosterone treatment induced lobe-specific pathology in mouse prostate.
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.
  
  
  CONCLUSIONS
  These data demonstrate that murine prostate is significantly and directly influenced by corticosterone treatment via aberrant stromal-to-epithelial growth factor signaling.
authors: Department of Andrology, ANZAC Research Institute, University of Sydney, Sydney, NSW, Australia. usimanainen@anzac.edu.au
authors: Ulla
authors: U
authors: Simanainen
authors: Anita
authors: A
authors: Lampinen
authors: Holger
authors: H
authors: Henneicke
authors: Tara C
authors: TC
authors: Brennan
authors: Uta
authors: U
authors: Heinevetter
authors: D Tim
authors: DT
authors: Harwood
authors: Keely
authors: K
authors: McNamara
authors: Markus
authors: M
authors: Herrmann
authors: Markus J
authors: MJ
authors: Seibel
authors: David J
authors: DJ
authors: Handelsman
authors: Hong
authors: H
authors: Zhou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003345:Corticosterone / Q000097:blood / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000187:drug effects* / Q000473:pathology; D011944:Receptors, Androgen / Q000032:analysis; D011965:Receptors, Glucocorticoid / Q000032:analysis
chemical_list: D011944:Receptors, Androgen; D011965:Receptors, Glucocorticoid; D003345:Corticosterone