staticnrg Posted January 6, 2007 Report Share Posted January 6, 2007 For those of you who have high levels of ACTH, this article may explain some things that are going on: Increased ERK phosphorylation in the adrenal gland in response to chronic ACTH treatment Full article available temporarily. Increased ERK phosphorylation in the adrenal gland in response to chronic ACTH treatmentJorge G Ferreira1,3, C?lia D Cruz2,3, Delminda Neves1,3 and Duarte Pignatelli1,3 1Laboratory of Molecular Cell Biology, Faculty of Medicine of Porto, Porto, Portugal 2Institute of Histology and Embryology, Faculty of Medicine of Porto, Porto, Portugal 3Instituto de Biologia Molecular e Celular (IBMC), Porto, Portugal (Requests for offprints should be addressed to D Pignatelli) (Current address of D pignatelli is at IPATIMUP, Porto, Portugal) -------------------------------------------------------------------------------- Abstract ACTH released from the pituitary acts through activation of cAMP/PKA in adrenocortical cells stimulating steroidogenesis. Although ACTH was originally thought to have anti-proliferative effects on the adrenal, recently it has been described that it could also have proliferative effects acting via other signalling cascades. This is also relevant in humans given the increased levels of ACTH occurring together with adrenal cortex hyperplasia observed in Cushing's disease (CD) and possibly in other situations such as chronic stress. One of the signalling pathways regulating cell proliferation is the ERKs pathway. ERKs are members of the MAPK family of cascades. They are activated by extracellular stimuli such as growth factors and mitogens, become phosphorylated via MEK1/2 and regulate a diversity of cellular processes such as proliferation and differentiation. Until now no study addressed the effects of chronic ACTH administration on the activation of ERKs in vivo. Objectives: Using rats submitted to different ACTH dosages as well as variable durations, we determined if ACTH induced ERKs activation and by establishing a parallelism with Proliferating Cell Nuclear Antigen (PCNA) expression we aimed to demonstrate a role of ACTH induced ERKs activation in cell proliferation. Blood was collected for hormonal analysis and the role of ACTH induced ERKS activation in the stimulation of steroidogenesis was also studied. We confirmed that ACTH increased adrenal weight and Corticosterone levels when compared with Control or Dexamethasone-treated animals. We also demonstrated that ACTH increases ERKs activation and PCNA expression in a time- and dose-dependent manner. When ERKs activation was blocked by the use of a specific MEK inhibitor (PD98059), there was a decrease in ACTH-induced Corticosterone release and PCNA expression. We conclude that chronic ACTH induces ERKs activation and that this plays an important role in the induction of cell proliferation as well as steroidogenesis. Journal of Endocrinology Quote Link to comment Share on other sites More sharing options...
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