Postdoctoral researcher University of Liege, GIGA-Molecular Biology of Diseases Liege, Belgium
Dayana Abboud (University of Liege, GIGA-Molecular Biology of Diseases)| Adrian Daly (University of Liege, Centre Hospitalier Universitaire de Liège)| Nadine Dupuis (University of Liege, GIGA-Molecular Biology of Diseases)| Mohamed Ali Bahri (University of Liege, GIGA-CRC In Vivo Imaging)| Asuka Inoue (Tohoku University, Graduate School of Pharmaceutical Sciences)| Andy Chevigné (Luxembourg Institute of Health, Immuno-Pharmacology and Interactomics, Department of Infection and Immunity)| Fabien Ectors (University of Liege, GIGA - Transgenics Platform)| Alain Plenevaux (University of Liege, GIGA-CRC In Vivo Imaging)| Bernard Pirotte (University of Liege, Laboratory of Medicinal Chemistry, Centre for Interdisciplinary Research on Medicines (CIRM))| Albert Beckers (University of Liege, Centre Hospitalier Universitaire de Liège)| Julien Hanson (University of Liege, GIGA-Molecular Biology of Diseases, University of Liege, GIGA-Molecular Biology of Diseases)
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). We report that Gpr101 causes elevated GH/prolactin secretion in transgenic GhrhrGpr101mice. We also show that GPR101 promotes GH secretion through the activation of not only Gs, but also Gq/11, in a PKA and PKC-dependent manner, respectively. Interestingly, in stark contrast with other Gs-coupled receptors, GPR101 activation did not lead to the proliferation of somatotrope cells.These signatures of GPR101 signaling, notably PKC activation, are also present in human X-LAG pituitary tumors with high GPR101 expression. These results underline a role for GPR101 in the regulation of somatotrope axis function.