>>5698868 This review article discusses a novel nontraditional site of estrogen synthesis and the potential targets of estrogen action within the male reproductive system. Our laboratories have recently demonstrated that developing spermatids in several species contain aromatase, the cytochrome P450 enzyme responsible for converting androgens into estrogens. The enzyme was localized by immunocytochemistry and the protein's presence was confirmed by Western blot analysis. Northern blot analysis and in situ hybridization were used to corroborate the presence of mRNA for aromatase. It appears that the aromatase message precedes the synthesis of the protein, and the protein remains in the spermatids several days after the message disappears. The enzyme is located along the tail of newly released sperm and is active in the epididymal sperm as well as in the developing germ cells of the testis. This unique discovery is the basis for our overall hypothesis that estrogen, synthesized by sperm, plays a role in the regulation of epididymal function proportional to the number of sperm being transported. The presence of an estrogen source within the ductal lumen is of special importance to the study of epididymal function because the regulatory mechanisms in this region remain unclear, particularly for the efferent ductules and initial segment regions, although estrogen receptors have been identified in the ductal epithelium. An understanding of the role that estrogen plays in the function of the epididymis may provide benefits in several areas including the treatment of abnormalities in epididymal function, the potential development of a male contraceptive, and insight into the causes of adult epididymal lesions induced by neonatal exposure to estrogenic compounds such as diethylstilbestrol.
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