The metaplastic effects of estrogen on mouse prostate epithelium: proliferation of cells with basal cell phenotype.
The exogenous administration of estrogens to male mice alters the hypothalamic-pituitary-gonadal axis and reduces androgen levels, leading to a regression of the prostatic epithelium. As well, a specific direct response to estrogens is the induction of epithelial squamous metaplasia. The aims of this study were to identify the process by which the prostatic epithelium is transformed in intact adult male mice using the synthetic estrogen, diethylstilbestrol. A comparison of the effects of diethylstilbestrol in the three lobes revealed a hierarchy of response, with the anterior lobe being the most responsive, the dorsolateral lobe less responsive, and the ventral lobe the least responsive. The effect of castration was used to distinguish between the epithelial responses to estrogen administration and androgen deprivation. The results demonstrate that transformation of the epithelium involved proliferation of cells with a basal cell phenotype, the onset of cytokeratin 10 expression, up-regulation of progesterone receptor expression, and loss of the cell cycle inhibitor, p27(Kip1) expression; none of these changes was observed after castration. Mice lacking functional estrogen receptor alpha failed to respond, demonstrating a requirement for estrogen receptor alpha in the epithelium and/or stroma to mediate the proliferative response to estrogen in the prostate gland.
Risbridger
G P
GP
Institute of Reproduction and Development, Monash Medical Center, Clayton, Melbourne, Victoria 3168, Australia. gail.risbridger@med.monash.edu.au
Wang
H
H
Frydenberg
M
M
Cunha
G
G
D000818:Animals; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000187:drug effects; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004054:Diethylstilbestrol / Q000494:pharmacology*; D004847:Epithelial Cells / Q000737:chemistry / Q000187:drug effects; D047628:Estrogen Receptor alpha; D007633:Keratins / Q000032:analysis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000032:analysis; D009919:Orchiectomy; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011467:Prostate / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D011960:Receptors, Estrogen / Q000032:analysis / Q000172:deficiency; D011980:Receptors, Progesterone / Q000032:analysis; D025521:Tumor Suppressor Proteins
C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D047628:Estrogen Receptor alpha; D008869:Microtubule-Associated Proteins; D018809:Proliferating Cell Nuclear Antigen; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D007633:Keratins; D004054:Diethylstilbestrol