Fetal Distribution of 5α-Reductase 1 and 5α-Reductase 2, and Their Input on Human Prostate Development

Abstract

Human prostate development starts in the tenth week of gestation. Initial interactions between the epithelium and mesenchyma are stimulated by androgens. The transformation of circulating testosterone to 5alpha-dihydrotestosterone by tissue linked 5alpha-reductase is a key event in androgen metabolism. The 5alpha-dihydrotestosterone mediates androgen effects in the urogenital sinus and external genitalia, leading to the formation of a male phenotype and androgen mediated prostate growth. Supposedly 5alpha-reductase 2 is the predominant isoenzyme in human accessory sex tissue, whereas the function of 5alpha-reductase 1 remains unclear. We focused on the detection, distribution and effects of the 2 isoenzymes during gestation and infancy. Serial sections from fetuses and infants were immunostained using antibodies directed against 5alpha-reductase 1 and 2. Additionally, to detect the downstream products of androgen synthesis reverse transcriptase-polymerase chain reaction analyses were done for 17 beta-hydroxysteroid dehydrogenase types 2, 3 and 7. Immunohistochemistry revealed positive staining for each isoenzyme throughout fetal development. Moreover, reverse transcriptase-polymerase chain reaction for 5alpha-reductase 1 and 2 confirmed these findings on the transcription level. Additionally, the most relevant enzymatic downstream products of cellular androgen synthesis (17 beta-hydroxysteroid dehydrogenase 2, 3 and 7) were also detected by reverse transcriptase-polymerase chain reaction. To our knowledge this is the first study revealing the expression and distribution of each 5alpha-reductase isoenzyme as well as the potential contribution of 5alpha-reductase 1 during fetal human prostate development.