5-alpha-reductase and the development of the human prostate

Abstract

During the 10th week of gestation human prostate development is about to start. Androgens are the crucial factors to stimulate the initial interactions between the epithelium and mesenchyme. One of the key events in androgen metabolism is the transformation of circulating testosterone to 5α-dihydrotestosterone (DHT) by tissue-linked 5α-reductase. Both, the formation of a male phenotype and the androgen-mediated growth of the prostate are mediated by DHT. To date the function of 5α-reductase 1 (5αR1) still remains unclear whereas 5α-reductase 2 (5αR2) is supposed to be the predominant isoenzyme in human accessory sex tissue. Only little data are available on the detection, distribution, and effects of both isoenzymes during fetal life and infancy. Recently, immunohistochemical investigations of serial sections from fetuses and infants using specific antibodies directed against 5αR1 and 5αR2 seem to shed light on that issue. Moreover, the detection of downstream products of androgen synthesis using RT-PCR analyses for 17-β hydroxysteroid dehydrogenase Type 2 (17 βHSD 2), 17 βHSD Type 3 and 17 βHSD Type 7 adds to discovering the molecular biological background. New studies confirm that both isoenzymes are present throughout fetal development. On the transcriptional level RT-PCR for 5αR1 and 5αR2 certifies these findings. 17 βHSD 2, 3 and 7 representing the most relevant enzymatic downstream products of cellular androgen synthesis were revealed by RT-PCR as well. Current studies discovered the expression and distribution of both 5α-reductase isoenzymes as well as the potential contribution of 5αR1 during fetal human prostate development.