Regulation of androgen and vitamin d receptors by 1,25-dihydroxyvitamin D3 in human prostate epithelial and stromal cells.
OBJECTIVE
The mechanisms of the interaction between 1,25-dihydroxyvitamin D(3) (1,25 D) and androgens, and their respective receptors in their action on the prostate are not completely understood. We examined the interplay of 1,25 D and androgens on the epithelial and stromal cells of the prostate.


METHODS
The human neonatal prostatic epithelial cell line 267B-1 (BRFF, Inc., Ijamsville, Maryland) and primary cultures of human prostate stromal cells were treated with medium containing 5 or 10 microM 1,25 D or ethanol (control) in the presence or absence of 10 nM dihydrotestosterone (DHT) (Sigma Chemical Co., St. Louis, Missouri). Protein levels of androgen receptor (AR) and vitamin D receptor (VDR) were determined by immunoblot analysis of whole cell extracts. Electrophoresis mobility shift assays were used to determine AR and VDR DNA binding activities.


RESULTS
The VDR protein level of 267B-1 cells was increased in the presence of 1,25 D (with the maximum effects seen at 24 hours) regardless of the presence or absence of DHT. In addition, exogenous DHT increased the AR and VDR DNA binding activities of 267B-1 and stromal cells in the presence of 1,25 D.


CONCLUSIONS
ARs in the normal prostate are regulated by androgens, whereas VDRs in the normal prostate can be regulated by 1,25 D as well as by other androgens such as testosterone. This finding further supports the concept that 1,25 D as a steroid hormone, in addition to other androgens such as DHT, may have a role in the growth and differentiation of normal prostate.
Leman
Eddy S
ES
Department of Urology, Cellular and Molecular Pathology Training Program, Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
DeMiguel
Fernando
F
Gao
Allen C
AC
Getzenberg
Robert H
RH
D002117:Calcitriol / Q000494:pharmacology*; D002478:Cells, Cultured; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D015151:Immunoblotting; D008297:Male; D010766:Phosphorylation; D011467:Prostate / Q000166:cytology* / Q000187:drug effects*; D011944:Receptors, Androgen / Q000187:drug effects*; D018167:Receptors, Calcitriol / Q000187:drug effects* / Q000378:metabolism; D017154:Stromal Cells / Q000187:drug effects
D011944:Receptors, Androgen; D018167:Receptors, Calcitriol; D002117:Calcitriol