Research Summary of the Role of Vitamin D in Prostatic Neoplasia

The prostate is a small organ of the male reproductive system located beneath the bladder which causes a significant number of problems with age. It is composed primarily of stromal cells and epithelial cells. An increase in cell growth within the stromal population of the prostate which is non-cancerous but can constrict the flow of urine through the urethra is called benign prostatic hyperplasia (BPH)

  1. One in four males will undergo surgery to improve urinary outflow as a result of this type of obstruction. A change in epithelial cells, detected usually by PSA level, may signal the beginning of prostate cancer. An increase in abnormal epithelial cell growth has been shown to be inhibited by vitamin D.

  2. and further evidence has shown it may even serve as a differentiating factor. The effect of vitamin D on stromal cell populations is less well known. The goal of our research with vitamin D is to determine the effect of this steroid hormone on normal prostate tissue. Our hypothesis is that 1,25-D (the active form of vitamin D) functions in the normal growth and if ferentiation of the human prostate, and works in combination with testosterone to regulate this organ. We have taken three approaches to establish the role of vitamin D in the prostate:

    1. to study the vitamin D receptor presence in human tissues and its role in BPH.
    2. to investigate the role of vitamin D in the promotion of growth or differentiation in human primary prostate cultures in defined media.
    3. to study the effect of vitamin D on the developing prostate.

    So far our studies have demonstrated that vitamin D reduces the epithelial cell population by 60% at a concentration of .01 uM. This result compares favorably with non-cancerous prostate studies in intact rats.

  3. The 1,25-D had a selective regressive effect on epithelial cells; however, 1,25-D stimulated stromal growth in the prostate. In the absence of testosterone, 1,25-D may exert a growth promoting effect on prostatic stroma in vivo. The interaction of vitamin D on prostate cells in the presence and absence of testosterone need to be addressed as well as the combined effects of 1,25-D and testosterone on stromal and epithelial cell populations in a chemically-defined medium.

  4. It is necessary to understand the action of 1,25D on normal human prostate cells, in order to develop this agent as an effective tool in prostate cancer therapy.

References:

  1. Oesterling, J.E. Benign prostatic hyperplasia: a review of its histogenesis and natural history. Prostate 6:67-73, 1996.
  2. Peehl, D.M., Skowronski, R.J., Leung, G.K., Wong, S.T., Stamey, T.A., and Feldman, D. Antiproliferative effects of 1,25-Dihydroxyvitamin D3 on primary cultures of human prostatic cells. Canc.Res.54: 805-810, 1994.
  3. Konety, B.R.; Schwartz, G.G.; Acierno, J.; Becich, M.J.; Getzenberg, R.H. The role of Vitamin D in normal prostate growth and development. Cell Growth Differ. 7:1563-1570, 1996.
  4. Krill, D.; Shuman, M.; Thompson, M.T.; Becich, M.J. ; Strom, S.C. A simple method for the isolation and culture of epithelial and stromal cells from benign and neoplastic prostates. Urology 49(6):981-988, 1997.

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