Roles for Hedgehog signaling in androgen production and prostate ductal morphogenesis
Autor: | Cory Abate-Shen, David M. Berman, Nishita Desai, Philip A. Beachy, Sunil S. Karhadkar, Melissa Reynon, Michael M. Shen, Xi Wang |
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Rok vydání: | 2004 |
Předmět: |
Male
Organogenesis Mice chemistry.chemical_compound Pregnancy Prostate Morphogenesis Sonic hedgehog In Situ Hybridization Mice Knockout biology Reverse Transcriptase Polymerase Chain Reaction Endoderm Veratrum Alkaloids Gene Expression Regulation Developmental Dihydrotestosterone Immunohistochemistry Hedgehog signaling pathway Cell biology medicine.anatomical_structure embryonic structures Androgens Female Prostate induction Triolein Signal Transduction medicine.drug medicine.medical_specialty animal structures Cyclopamine medicine.drug_class Tissue recombination Ductal morphogenesis Internal medicine medicine Animals Hedgehog Proteins Molecular Biology Hedgehog DNA Primers Cell Biology Androgen Endocrinology chemistry Trans-Activators biology.protein Developmental Biology |
Zdroj: | Developmental Biology. 267:387-398 |
ISSN: | 0012-1606 |
Popis: | Previous studies have demonstrated that the Hedgehog (Hh) signaling pathway plays a critical role in the development and patterning of many endodermally derived tissues. We have investigated the role of Sonic hedgehog (Shh) in formation of the prostate gland by examining the urogenital phenotype of Shh mutant fetuses. Consistent with earlier work reporting an essential role for Shh in prostate induction, we have found that Shh mutant fetuses display abnormal urogenital development and fail to form prostate buds. Unexpectedly, however, we have discovered that this prostate defect could be rescued by three different methods: renal grafting, explant culture in the presence of androgens, and administration of dihydrotestosterone (DHT) to pregnant mice, indicating that the prostate defect in Shh mutants is due to insufficient levels of androgens. Furthermore, we find that the inhibition of Hh pathway signaling by treatment with cyclopamine does not block prostate formation in explant culture, but instead produces morphological defects consistent with a role for Hh signaling in ductal patterning. Taken together, our studies indicate that the initial organogenesis of the prostate proceeds independently of Shh, but that Shh or other Hh ligands may play a role in subsequent events that pattern the prostate. |
Databáze: | OpenAIRE |
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