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

Dayana Abboud, Adrian F. Daly, Nadine Dupuis, Mohamed Ali Bahri, Asuka Inoue, Andy Chevigné, Fabien Ectors, Alain Plenevaux, Bernard Pirotte, Albert Beckers, Julien Hanson

研究成果: Article査読

5 被引用数 (Scopus)

抄録

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.

本文言語English
論文番号4752
ジャーナルNature communications
11
1
DOI
出版ステータスPublished - 2020 12 1

ASJC Scopus subject areas

  • 化学 (全般)
  • 生化学、遺伝学、分子生物学(全般)
  • 物理学および天文学(全般)

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