The long-term objectives of this study are: 1) to establish the role of prolactin in the etiology and progression of prostate cancer in man; 2) to determine whether prolactin-secretion inhibitors are useful as chemotherapeutic agents alone or in combination therapy for prostate cancer and 3) to investigate whether natural agents like vitamin D, which also inhibit prolactin secretion, may be useful in the prevention of prostate cancer. Three hypotheses will be tested: 1) that prolactin enhances the growth of malignant prostatic epithelial cells; 2) that this stimulatory effect is specific to prolactin and that other anterior pituitary hormones (GH, FSH, TSH and LH) do not produce the same effect and 3) that prolactin, in combination with 5Alpha-dihydrotestosterone (5Alpha-DHT) and 17Beta-estradiol (17Beta-E), enhances the growth of prostatic epithelium. In vitro cell systems, consisting of DU-145 and PC-3 human prostatic carcinoma cell lines and Dunning R3327 rat prostate adenocarcinoma cells, will be used. In vitro studies will determine whether prolactin alters growth and whether the effects are species specific and biphasic. Preliminary studies suggest growth enhancement of prostate carcinoma cells by prolactin. Effects on GH, FSH, TSH, and LH on growth alone and in combination with prolactin will be studied to determine whether the growth-enhancing effects of prolactin are specific to prostatic epithelium. Hormone interactions involving prolactin, 5Alpha-DHT and 17Beta-E will be examined to determine whether their effects on growth are additive, synergistic or antagonistic. In vivo, prolactin appears to enhance 5Alpha-DHT action on prostate cells. The in vitro studies propose to dissect and separate these hormone actions and interactions, which may play a role in the etiology and progression of prostate cancer in man. Clonal growth assay, cell number, DNA, RNA and protein content and prolactin receptor measurements will be used to assess hormone interactions and their effects on cell growth. The proposed studies will make significant contributions in the area of etiology, prevention, intervention and treatment of prostate cancer.
