TY - JOUR
T1 - Regulation of androgen and vitamin D receptors by 1,25-dihydroxyvitamin D3 in human prostate epithelial and stromal cells
AU - Leman, Eddy S.
AU - DeMiguel, Fernando
AU - Gao, Allen C
AU - Getzenberg, Robert H.
PY - 2003/7/1
Y1 - 2003/7/1
N2 - Purpose: The mechanisms of the interaction between 1,25-dihydroxyvitamin D3 (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. Materials and 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 μM 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.
AB - Purpose: The mechanisms of the interaction between 1,25-dihydroxyvitamin D3 (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. Materials and 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 μM 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.
KW - Androgens
KW - Calcitriol
KW - Prostate
KW - Receptors, androgens
KW - Steroids
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U2 - 10.1097/01.ju.0000060117.61770.35
DO - 10.1097/01.ju.0000060117.61770.35
M3 - Article
C2 - 12796696
AN - SCOPUS:0037664958
VL - 170
SP - 235
EP - 240
JO - Journal of Urology
JF - Journal of Urology
SN - 0022-5347
IS - 1
ER -