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BACKGROUND While the androgen‐dependence of the prostate gland has long been accepted, the participation of estrogen, mediated via the stroma in the elicitation of benign prostatic hyperplasia (BPH), has only recently been recognized. Its mode of action is still uncertain. METHODS This review first outlines the regulation of gene expression via hormones, growth factors, and other ligands in the coordination of cell growth, differentiation, and function. Focus is next directed to factors particularly involved in phosphorylation of estrogen receptors. Then, the access of sex steroids, especially of estrogen to the cell and to the transduction machinery, is described, preparatory to examining the hypotheses by which this access causes the process of BPH to occur. RESULTS It becomes clear that the necessary phosphorylative activities which transmit signals to nuclear receptors and thence transcription of target genes can be performed by steroids or mimicked by proxy molecules and by cross‐talk between discrete pathways. The character and concentration of the available estrogen are determined by the extent of its biosynthesis, its penetration of the cell, and its subsequent metabolism. In addition, the estrogen affects its own access through stimulation of facilitating peptide hormones, prolactin, and sex hormone‐binding globulin. Finally, the induction of BPH is shown to be determined by the androgen/estrogen ratio and the change in stromal/epithelial balance accompanying aging. CONCLUSIONS Despite a growing knowledge of hormone levels, metabolism, and activities in the prostate, and the variety of processes and factors they affect, our explanation of BPH is still fanciful. Prostate 41:263–274, 1999. © 1999 Wiley‐Liss, Inc.

Three experiments were performed to determine whether human prolactin (hPr) affects prostatic uptake and metabolism of testosterone (T). 1) Patients with prostatic cancer were infused twice with radio-labelled androgens, the first time with basal hPR, the second time with oral thyrotrophin-releasing hormone (TRH)-elevated hPr. In 5/7, significant increases in metabolic clearance of dihydrotestosterone (DHT) and in conversion of T to DHT accompanied increased hPR. 2) The incorporation of labelled T into minced benign prostatic hypertrophy (BPH) tissue from subjects with high (40 ng/ml) hPR was measured and was found to be more than twice the uptake into tissue from those with low hPR (6.5 +/- 1.9 ng/ml). 3) Uptake and metabolism in vivo of a bolus of 3H-T by BPH and carcinomatous prostates was measured and was far greater in subjects whose hPR was elevated by chlorpromazine than in untreated controls. It is concluded that prolactin increases prostatic uptake and metabolism of T. It is suggested that the best management of prostatic cancer should include depletion of prolactin as well as androgen.