Estrogens influence the physiology of many organs by activation of the nuclear receptors ERalpha and ERbeta. The epithelium of ventral prostate, ovarian granulosa cells and lung, are ERalpha-negative but express high levels of ERbeta. This thesis focuses on the role played by ERbeta in ERalpha-negative epithelium. The prostate is of medical interest because it is very frequently the site of malignancy in elderly men. Prostate cancer is the most lethal form of cancer in men after lung cancer. We studied the ventral prostate of mice to gain insight into the role of ERbeta in prostatic epithelium. We used histochemical, protein profiling and FACS analysis to study the ventral prostate of mice in which ERbeta gene has been inactivated (ERbeta−/− mice). We found epithelial hyperplasia, accumulation undifferentiated epithelial cells and dysregulation of several proteins associated to low differentiation level. Among these proteins, serine protease inhibitor Kazal type 3, called Spink3. The human homologous of Spink3, TATI, is positively related to low epithelial differentiation grade (Gleason Score) in human prostate cancer. Analyzing prostate cancer biopsies of patients at different Gleason Scores we observed a negative correlation between TATI and ERbeta expression and positive correlation between TATI and Gleason Score. This study showed a role for ERbeta in differentiation of the prostatic epithelium in mice and man. The granulosa cells of the ovarian follicle are epithelial-derived cells which secrete estradiol. which is essential for maturation of the ovum, and preparation of the entire body for response to a fertilized ovum. In the ovarian follicles ERbeta is abundantly expressed in the nuclei of granulosa cells, while the theca cells are ERalpha-positive and ERbeta-negative. Theca cells are stromal-derived cells which form a highly vascularized layer surrounding the granulosa cells during follicular maturation. Female of ERbeta−/− mice vary rarely ovulate and are considered to be subfertile. In the ovary, ...