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

Abstract

During the 10(th) 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 5alpha-dihydrotestosterone (DHT) by tissue-linked 5alpha-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 5alpha-reductase 1 (5alphaR1) still remains unclear whereas 5alpha-reductase 2 (5alphaR2) 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 5alphaR1 and 5alphaR2 seem to shed light on that issue. Moreover, the detection of downstream products of androgen synthesis using RT-PCR analyses for 17-beta hydroxysteroid dehydrogenase Type 2 (17 betaHSD 2), 17 betaHSD Type 3 and 17 betaHSD 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 5alphaR1 and 5alphaR2 certifies these findings. 17 betaHSD 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 5alpha-reductase isoenzymes as well as the potential contribution of 5alphaR1 during fetal human prostate development.

Keywords: 5-alpha-reductase; fetal development; human prostate.

Figure 1

(A and B) Expression of 5αR1 and 5αR2 in the fetal prostate (magnification 400×): (A) Within the epithelium 5αR1 is primarily found while only few scattered cells are identified in the stroma (21^st week); (B) 5αR2 exhibits a much weaker staining intensity in the epithelial compartment whereas it is significantly more abundant in stromal cells (27^th week)

Figure 2

(A and B) Expression of 5αR1 and 5αR2 at the end of gestation and postnatally (magnification 400×): (A) At the end of gestation 5αR1 is particularly accumulated within the epithelium with a small number of positively stained cells in the stroma; (B) Postnatal at the age of five months stromal staining can be clearly detected for 5αR2 being more intense than for 5αR1