The prostate is a complex organ which has been demonstrated to be regulated by androgens, stroma-epithelial interactions, growth factors and other components. While androgens and androgen receptors have been demonstrated to be essential to prostate growth, androgen action alone cannot account for all of the aspects of prostatic regulation and, therefore, studies are needed to define and characterize other effectors. In addition to androgen receptors, receptors for other members of the steroid hormone superfamily have been identified in the prostate. Vitamin D is a member of this hormone family and has been demonstrated to have receptors in the prostate. Currently, data from several laboratories have demonstrated that vitamin D is able to influence the growth and differentiation of prostate cancer cells. We present data in this application in which we demonstrate that vitamin D has an androgen influenced role in the regulation of prostatic growth and differentiation in the rat. In the absence of testosterone, vitamin D caused a 2.4 fold increase in stroma and a regression of the epithelium. In the presence of testosterone, vitamin D induced increased differentiation of the epithelium. In addition, we have demonstrated that the immuno-histochemical detection of vitamin D receptors, may not reveal differences in receptor forms that we have identified in the rat prostate and testes. Based on our preliminary data, as well as available literature, we hypothesize that vitamin D, as a steroid hormone, has a role in the normal growth and differentiation of the human prostate and in combination with testosterone and other effectors regulates this organ. We will translate our preliminary data developed in the rat to address important issues in the human prostate, such as normal and abnormal growth and interactions of vitamin D with androgen. We propose to test this hypothesis by carrying out the following specific aims: (1) to determine the distribution of the postulated isoforms of the vitamin D receptor in human prostate tissue of various ages and androgen states and to investigate the vitamin D receptor in benign prostatic hyperplasia (BPH); (2) to investigate the ability of vitamin D to promote the growth and/or differentiation of human primary cultures of stromal and epithelial cells; and (3) to determine the in vivo effects of vitamin D on the growth and differentiation of the developing prostate. These studies are likely to reveal important information about the role of vitamin D and its interplay with androgens in the normal prostate and in BPH.
