Basal adrenocorticotropin (ACTH) secretion is negatively modulated by protein phosphatase 5 in mouse pituitary corticotropin AtT20 cells.
siRNA oligonucleotides for protein phosphatase 5 (PP5) were designed and transfected into mouse corticotroph AtT20 cells to induce lower PP5 expression levels. PP5-siRNA transfections (at 3 days) produced a approximately 50% down-regulation in targeted protein levels. PP5-underexpressing cells released significantly more ir-ACTH (10-12-fold) relative to baseline levels and promoted POMC release into the media. Neither CRF-mediated ACTH release nor dexamethasone-induced ACTH repression were affected in PP5-siRNA transfected cells. In summary, our observations suggest that endogenous PP5 can exert a negative modulatory effect on basal ACTH release in neurosecretion-competent AtT20 cells through a mechanism as yet unknown but which does not directly involve regulated CRF or glucocorticoid receptor-dependent pathways. However, PP5 may cause mis-sorting of POMC and POMC-derived peptides at the constitutive-like secretory pathway level in an unregulated manner. Such a missorting could lead to impaired processing of POMC.
Liu
Feng
F
Department of Neuroscience, Wyeth Research, 865 Ridge Road, Monmouth Junction, NJ 08852, USA.
Khawaja
Xavier
X
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D010902:Pituitary Gland / Q000166:cytology*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism
D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D010749:Phosphoprotein Phosphatases; C089641:protein phosphatase 5