GPR101 drives growth hormone hypersecretion and gigantism in mice via constitutive activation of G s and G q/11

Growth hormone (GH) is a key modulator of growth and GH over-secretion can lead to gigantism. One form X-linked acrogigantism (X-LAG), in which infants develop secreting pituitary tumors over-expressing the orphan G-protein coupled receptor, GPR101. The role GPR101 secretion remains obscure. We studied signaling pathways their effects HEK293 rat GH3 cell lines, human transgenic mice with elevated somatotrope Gpr101 expression driven by Ghrhr promoter (GhrhrGpr101). report that causes GH/prolactin GhrhrGpr101mice. also show promotes through activation not only Gs, but Gq/11, PKA PKC-dependent manner, respectively. Interestingly, stark contrast other Gs-coupled receptors, did proliferation cells. These signatures signaling, notably PKC activation, are present X-LAG high expression. results underline for regulation axis function.