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Mechanisms for luteinizing hormone induction of growth hormone gene transcription in fish model: Crosstalk of the cAMP/PKA pathway with MAPK-and PI3K-dependent cascades

Sun, Caiyun, He, Mulan, Ko, Wendy K.W., Wong, Anderson O.L.
Molecular and Cellular Endocrinology 2014 v.382 pp. 835-850
Ctenopharyngodon idella, adenylate cyclase, autocrine signaling, cAMP-dependent protein kinase, carp, cyclic AMP, gene expression, human chorionic gonadotropin, luteinizing hormone, luteinizing hormone receptors, mitogen-activated protein kinase, models, phosphatidylinositol 3-kinase, phosphorylation, secretion, somatotropin, transcription (genetics)
In our previous studies in grass carp pituitary cells, local production of luteinizing hormone (LH) was shown to induce growth hormone (GH) production and gene expression, which constitutes a major component of the “intrapituitary feedback loop” regulating GH secretion and synthesis via autocrine/paracrine interactions between gonadotrophs and somatotrophs in the carp pituitary. To further investigate the signaling mechanisms mediating LH action at the transcriptional level, promoter studies were performed in GH3 cells co-transfected with the expression vector for carp LH receptor and luciferase-expressing reporter constructs with grass carp GH promoter. In this cell model, treatment with human chorionic gonadotropin (hCG) was effective in increasing GH promoter activity and the responsive sequence was mapped to position −616 and −572 of the grass carp GH promoter. GH promoter activation induced by hCG occurred with concurrent rise in cAMP production, CREB phosphorylation, and could be inhibited by inactivation of adenylate cyclase (AC), PKA, MEK1/2, P38 MAPK, PI3K and mTOR. AC activation, presumably via cAMP production, could mimic hCG-induced CREB phosphorylation and GH promoter activity, and these stimulatory effects were also sensitive to the blockade of PKA-, MAPK- and PI3K- dependent cascades. These results, as a whole, suggest that LH receptor activation in the carp pituitary may trigger GH gene transcription through CREB phosphorylation as a result of the functional crosstalk of the cAMP/PKA pathway with MAPK-and PI3K-dependent cascades.