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GPR101 drives growth hormone hypersecretion and gigantism in mice via constitutive activation of Gs and Gq/11

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Listed:
  • Dayana Abboud

    (University of Liège)

  • Adrian F. Daly

    (University of Liège)

  • Nadine Dupuis

    (University of Liège)

  • Mohamed Ali Bahri

    (University of Liège)

  • Asuka Inoue

    (Tohoku University)

  • Andy Chevigné

    (Luxembourg Institute of Health)

  • Fabien Ectors

    (Liège University)

  • Alain Plenevaux

    (University of Liège)

  • Bernard Pirotte

    (University of Liège)

  • Albert Beckers

    (University of Liège)

  • Julien Hanson

    (University of Liège
    University of Liège)

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 (GhrhrGpr101). Here, we report that Gpr101 causes elevated GH/prolactin secretion in transgenic GhrhrGpr101 mice but without hyperplasia/tumorigenesis. We show that GPR101 constitutively activates not only Gs, but also Gq/11 and G12/13, 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.

Suggested Citation

  • Dayana Abboud & Adrian F. Daly & Nadine Dupuis & Mohamed Ali Bahri & Asuka Inoue & Andy Chevigné & Fabien Ectors & Alain Plenevaux & Bernard Pirotte & Albert Beckers & Julien Hanson, 2020. "GPR101 drives growth hormone hypersecretion and gigantism in mice via constitutive activation of Gs and Gq/11," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18500-x
    DOI: 10.1038/s41467-020-18500-x
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