Vitamin D and androgen regulation of prostatic growth.
Vitamin D has been reported to inhibit the growth of prostate cancer cells and model systems. In this study, we examined the interaction between 1,25-dihydroxyvitamin D(3) (1,25 D) in the presence or absence of endogenous testosterone on the growth and development of the adult rat prostate. Male Sprague-Dawley rats (165 days old) were either kept intact or castrated. Seven days after castration, the rats were treated with vehicle (control) or 1,25 D for 3 weeks and then sacrificed. Both ventral and dorsal lateral prostates were harvested; whole tissue lysates were collected and AR and VDR protein levels were analyzed by immunoblot analyses. Administration of 1,25 D in the intact animals decreased the prostatic size by 40%, compared to control animals, whereas 1,25 D did not influence the size of the prostate in castrated rats. 1,25 D administration in intact groups also increased both the AR and VDR protein levels by approximately twofold, whereas in castrated groups, 1,25 D only increased the AR protein level by 1.5-2.5-fold. 1,25 D in the presence of endogenous testosterone inhibits prostatic growth, whereas 1,25 D in the absence of endogenous testosterone does not affect prostatic growth. The growth inhibitory activity of 1,25 D in the presence of testosterone may be mediated through the ligand activated AR and VDR pathways. These studies may reveal important information about the potential efficacy of 1,25 D as well as hormonal status in understanding the development of prostate diseases.
Leman
Eddy S
ES
Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15232, USA.
Arlotti
Julie A
JA
Dhir
Rajiv
R
Getzenberg
Robert H
RH
D000818:Animals; D002117:Calcitriol / Q000378:metabolism*; D002369:Castration; D008297:Male; D009929:Organ Size; D011467:Prostate / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism*
D011944:Receptors, Androgen; D018167:Receptors, Calcitriol; D013739:Testosterone; D002117:Calcitriol