Fetal distribution of 5α-reductase 1 and 5α-reductase 2, and their input on human prostate development

Purpose: 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 5 alpha-dihydrotestosterone by tissue linked 5 alpha-reductase is a key event in androgen metabolism. The 5 alpha-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 5a-reductase 2 is the predominant isoenzyme in human accessory sex tissue, whereas the function of 5a-reductase 1 remains unclear. We focused on the detection, distribution and effects of the 2 isoenzymes during gestation and infancy. Materials and Methods: Serial sections from fetuses and infants were immunostained using antibodies directed against 5 alpha-reductase 1 and 2. Additionally, to detect the downstream products of androgen synthesis reverse transcriptase-polymerase chain reaction analyses were done for 17 P-hydroxysteroid dehydrogenase types 2, 3 and 7. Results: Immunohistochemistry revealed positive staining for each isoenzyme throughout fetal development. Moreover, reverse transcriptase-polymerase chain reaction for 5a-reductase I and 2 confirmed these findings on the transcription level. Additionally, the most relevant enzymatic downstream products of cellular androgen synthesis (17 P-hydroxysteroid dehydrogenase 2, 3 and 7) were also detected by reverse transcriptase-polymerase chain reaction. Conclusions: To our knowledge this is the first study revealing the expression and distribution of each 5a-reductase isoenzyme as well as the potential contribution of 5a-reductase 1 during fetal human prostate development.