期刊
MOLECULAR AND CELLULAR ENDOCRINOLOGY
卷 371, 期 1-2, 页码 174-181出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2012.12.006
关键词
MAP kinase phosphatase; MKP-3; Human gonadotropin hormone; Leydig cells; ERK1/2; p21
资金
- Universidad de Buenos Aires [20020100100760, 20020090200500]
- Consejo Nacional de Investigaciones Cientificas y Tecnicas, CONICET [PIP 112-200801-00209, PIP 201101 00101, PIP 114-200901-00389]
Luteinizing hormone (LH) activates ERK1/2, MAP kinases (MAPKs) necessary for its action on steroidogenesis and cell proliferation, and also induces MAPK phosphatase-1 (MKP-1), which rapidly dephosphorylates nuclear ERK1/2. MKP-3 is a cytoplasmic ERK-phosphatase up-regulated by proliferative stimuli. MKP-3 also dephosphorylates transcription factor FOXO1, promoting its transport to the nucleus. Here we analyzed MKP-3 expression in MA-10 Leydig cells and demonstrated that LH receptor (LHR) activation with human gonadotropin hormone (hCG) and an analog of its second messenger, 8Br-cAMP, up-regulates MKP-3 by transcriptional and post-translational mechanisms. It is known that FOXO1 drives the expression of the cell cycle inhibitor p21. Since the activation of this transcription factor by MKP-3 has been reported, we assessed the effect of shRNA against MKP-3 on p21mRNA levels. 8Br-cAMP increased these levels (2-fold at 2 h) and MKP-3 down-regulation reduced this effect. Our work demonstrates that LH/hCG tightly up-regulates MKP-3 which in turn, dephosphorylates ERK1/2 and drives p21 expression. These events could contribute to counteract hormonal action on cell proliferation. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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