The human prostate expresses Sonic hedgehog during fetal development

Purpose: The keynote event of prostate ductal development is the formation of epithelial buds that invade the urogenital sinus mesenchyma. Studies in mice have shown that budding requires the signaling peptide Sonic hedgehog, which is expressed in the epithelium of the prostatic anlagen. We report our characterization of sonic hedgehog (SHH) expression in the human fetal prostate. Materials and Methods: Reverse transcriptase-polymerase chain reaction was performed in fetal prostate RNA isolated at 15.5 and 18 weeks of gestation, respectively. Immunostaining was performed on sections from 7 male fetuses at 9.5 to 34 and in 4 female fetuses at 9 to 18 weeks of gestation. Results: Weak staining for SHH was seen in the prostatic urethra at 9.5 weeks. Intense staining was seen at 11.5 and 13 weeks in the prostatic urothelium and nascent prostatic buds. Staining was slightly diminished at 16.5, further diminished at 18 to 20 and absent at 34 weeks. SHH expression at 15.5 and 18 weeks was confirmed by reverse transcriptase-polymerase chain reaction assay of freshly isolated prostate tissue. Comparative SHH immunostaining in the female showed urothelial staining at 9 and 12 weeks with staining greatest above the entrance of the mullerian ducts. Staining diminished earlier in the female (14 weeks) than in the male and was almost absent at 18 weeks. Conclusions: SHH expression in the human fetal prostate is contemporaneous with the fetal testosterone surge and with ductal budding of the prostatic urothelium. SHH expression is also present in the female urogenital sinus but in the absence of testosterone it is not associated with ductal budding.