Sonic and desert hedgehog signaling in human fetal prostate development

BACKGROUND. Hedgehog signaling is thought to play an important role in rodent prostate organogenesis and morphogenesis. However, the role of this signaling pathway in human fetal prostate development has not been investigated. METHODS. Twenty-five human fetal prostates at various developmental stages (1039 weeks) were included. Fifteen specimens were processed for H&E and immunohistochemical staining of the Hedgehog signaling components: Sonic Hedgehog (SHH), Desert Hedgehog (DHH), Patched-l(PTCl), Patched-2 (PTC2), Smoothened (SMO), GLI1, and proliferating cell nuclear antigen (PCNA). SHH, DHH, and GLI1 expression was also analyzed in ten snap-frozen specimens by Western blot. RESULTS. SHH, DHH, SMC, PTC1, GLI1, and PCNA expression, assessed by a semi-quantitative immunohistochemical method, was found mainly in the developing prostatic epithelial ducts, beginning at 10 weeks and peaking at 16 and 28 weeks with a dip occurring at 20 weeks, with the exception of PTC2. CONCLUSION. Both SHH and DHH signaling components were detected during human fetal prostate development. Despite the high expression of PTC2 in the epithelium as well as the stroma in the early time of development, the expression of SHH, DHH, SMO, PTC1, and a SHH/DHH target transcription factor, GLI-1, were all largely restricted to epithelium in the developing prostate, suggesting that SHH/DHH signaling is primarily through an autocrine mechanism in human fetal prostate organogenesis.