The Human Prostate Expresses Sonic Hedgehog During Fetal Development

Barnett, Daniel H.; Huang, Hongying; Wu, Xue-Ru; Laciak, Robert; Shapiro, Ellen; Bushman, Wade

doi:10.1097/00005392-200211000-00099

Cited by 3 publications

(2 citation statements)

References 16 publications

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“…Furthermore, by blocking the action of Shh in the mouse, prostate budding does not occur, another malformation associated with megalourethra [Podlasek et al, 1999]. In human fetuses, SHH expression coincides with prostate budding and fetal testosterone surge [Barnett et al, 2002]. Relative to defects seen in infants of mothers with diabetes, urogenital abnormalities, in addition to megalourethra, have been well described and range from urorectal septum malformation sequence and aphallia to hypospadius [Gripp et al, 1999; Aberg et al, 2001].…”

Section: Discussionmentioning

confidence: 99%

Megalourethra: A report of three cases associated with maternal diabetes and a review of the literature—is sonic hedgehog the common pathway?

Vaux

Jones

Benirschke

et al. 2004

American J of Med Genetics Pt A

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The mechanisms by which maternal diabetes causes malformations in the offspring have yet to be elucidated. The purpose of this report is twofold: first, to describe three male infants born with multiple congenital anomalies and megalourethra, a defect which has not been previously reported in infants of women with diabetes; and second, to indicate that the defects seen in association with megalourethra in these three infants are similar to those seen as a consequence of abnormalities in sonic hedgehog, suggesting that maternal diabetes may affect sonic hedgehog expression in susceptible tissues during critical stages of development.

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Section: Discussionmentioning

confidence: 99%

Megalourethra: A report of three cases associated with maternal diabetes and a review of the literature—is sonic hedgehog the common pathway?

Vaux

Jones

Benirschke

et al. 2004

American J of Med Genetics Pt A

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show abstract

“…Hedgehog (Hh) signaling, which plays an important role in embryonic development, 6 regulates development of the prostate 7 . The details of Hh signaling are still being unraveled.…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical analysis of Hedgehog signaling in prostatic adenocarcinoma

Kim

2011

Basic and Applied Pathology

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Background and aim: The Hedgehog (Hh) signaling pathway plays an essential role in normal development of normal prostate gland. Deregulation of this pathway is responsible for carcinogenesis of prostatic adenocarcinoma. Methods: Total 176 cases of prostatic adenocarcinomas were prepared and the Hh signaling molecules including Sonic hedgehog (Shh), Patched (Ptch), Smoothened (Smo), GLIoma-associated oncogene (Gli-1) and suppressor of fused (Su[fu]) were immunohistochemically analyzed. Results: Hh signaling molecules were significantly associated with prognostic factors; High Gleason score (≥7) was significantly associated with expression of Shh, Ptch, Smo, and Gli-1; tumor, node and metastasis stages with Shh, Ptch, Smo and Gli-1; initial prostate specific antigen with Ptch and Smo; large tumor volume with Gli-1; perineural invasion with Shh, Smo and Gli-1. Su(fu) was significantly associated inversely with multiplicity of tumor. Conclusions: Hh signaling molecules including Shh, Ptch, Smo and Gli-1 were associated with high Gleason score and advanced stage even in the low Gleason score.

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Sonic Hedgehog Activates Mesenchymal Gli1 Expression during Prostate Ductal Bud Formation

Lamm

Catbagan

Laciak

et al. 2002

Developmental Biology

158

177

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Ductal budding in the developing prostate is a testosterone-dependent event that involves signaling between the urogenital sinus epithelium (UGE) and urogenital sinus mesenchyme (UGM). We show here that ductal bud formation is associated with focused expression of Sonic hedgehog (Shh) in the epithelium of nascent prostate buds and in the growing tips of elongating prostate ducts. This pattern of localized Shh expression occurs in response to testosterone stimulation. The gene for the Shh receptor, Ptc1, is expressed in the UGM, as are the members of the Gli gene family of transcriptional regulators (Gli1, Gli2, and Gli3). Expression of Ptc1, Gli1, and Gli2 is localized primarily to mesenchyme surrounding prostate buds, whereas Gli3 is expressed diffusely throughout the UGM. A strong dependence of Gli1 (and Ptc1) expression on Shh signaling is demonstrated by induction of expression in both the intact urogenital sinus and the isolated UGM by exogenous SHH peptide. A similar dependence of Gli2 and Gli3 expression on Shh is not observed. Nonetheless, the chemical inhibitor of Shh signaling, cyclopamine, produced a graded inhibition of Gli gene expression (Gli1>Gli2>Gli3) in urogenital sinus explants that was paralleled by a severe inhibition of ductal budding.

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The Human Prostate Expresses Sonic Hedgehog During Fetal Development

Abstract: expression in the human fetal prostate is contemporaneous with the fetal testosterone surge and with ductal budding of the prostatic urothelium. expression is also present in the female urogenital sinus but in the absence of testosterone it is not associated with ductal budding.

Cited by 3 publications

References 16 publications

Megalourethra: A report of three cases associated with maternal diabetes and a review of the literature—is sonic hedgehog the common pathway?

Megalourethra: A report of three cases associated with maternal diabetes and a review of the literature—is sonic hedgehog the common pathway?

Immunohistochemical analysis of Hedgehog signaling in prostatic adenocarcinoma

Sonic Hedgehog Activates Mesenchymal Gli1 Expression during Prostate Ductal Bud Formation

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