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- W2623564938 abstract "Sonic hedgehog (Shh) is a signaling protein that binds to Patched and mediates its effects through Gli transcription factors. It is important in regulating survival and growth in both the embryo and the adult. During pituitary development, Shh is uniformly expressed throughout the oral ectoderm, but restricted from the Rathke's pouch as soon as it becomes morphologically visible. Shh signal transduction pathway has lately been implicated as one of the most important regulators of oncogenic transformation. Here we have tested the hypothesis that the Shh-Gli signaling pathway is implicated in the pathogenesis of pituitary adenomas. We studied the expression and function of Shh pathway members in 55 pituitary tumors compared to the normal pituitary. The studies were done at the mRNA level using RT-PCR and at the protein level using single/double immunohistochemistry. We found that Shh is secreted by the corticotrophs of the anterior pituitary. The Shh pathway is also active in other hormone secreting anterior pituitary cells, as demonstrated by the presence of its receptors Patched 1, Patched 2 and the transcription factor Gli1. Our results reveal a marked reduction of Shh in all types of pituitary adenomas compared to the normal pituitary gland. Interesting was the fact that although Shh is expressed in pituitary corticotrophs, it was found absent from all Cushing tumors studied (n=13). Shh at 5µg/ml reduces up to 50% the proliferation of AtT-20 murine corticotrophinoma cells in culture. We also found that Shh impact on the cell cycle is due to its effect in downregulating the protein levels of p27Kip1. We conclude that Shh might be necessary for the maintenance of a low/non proliferation state in the corticotrophs (also supported by development data). In the absence of Shh, corticotrophs proliferate more and this could be one of the reasons leading to adenoma formation." @default.
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- W2623564938 date "2005-03-21" @default.
- W2623564938 modified "2023-09-27" @default.
- W2623564938 title "Sonic hedgehog is implicated in the pathogenesis of corticotroph tumors" @default.
- W2623564938 doi "https://doi.org/10.1055/s-2005-862832" @default.
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