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• W3087441530 abstract "Abstract Growth hormone (GH) is a key modulator of growth and GH over-secretion can lead to gigantism. One form is X-linked acrogigantism (X-LAG), in which infants develop GH-secreting pituitary tumors over-expressing the orphan G-protein coupled receptor, GPR101. The role of GPR101 in GH secretion remains obscure. We studied GPR101 signaling pathways and their effects in HEK293 and rat pituitary GH3 cell lines, human tumors and in transgenic mice with elevated somatotrope Gpr101 expression driven by the rat Ghrhr promoter ( Ghrhr Gpr101 ) . Here, we report that Gpr101 causes elevated GH/prolactin secretion in transgenic Ghrhr Gpr101 mice but without hyperplasia/tumorigenesis. We show that GPR101 constitutively activates not only G s , but also G q/11 and G 12/13 , which leads to GH secretion but not proliferation. These signatures of GPR101 signaling, notably PKC activation, are also present in human pituitary tumors with high GPR101 expression. These results underline a role for GPR101 in the regulation of somatotrope axis function." @default.
• W3087441530 created "2020-09-25" @default.
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• W3087441530 date "2020-09-21" @default.
• W3087441530 modified "2023-09-26" @default.
• W3087441530 title "GPR101 drives growth hormone hypersecretion and gigantism in mice via constitutive activation of Gs and Gq/11" @default.
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• W3087441530 doi "https://doi.org/10.1038/s41467-020-18500-x" @default.
• W3087441530 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7506554" @default.
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