Role of mitogen-activated protein kinase in prostaglandin F2α action in human granulosa-luteal cells

Chen Jei Tai, Sung Keun Kang, Kyung Chul Choi, Chii Ruey Tzeng, Peter C K Leung

研究成果: 雜誌貢獻文章

34 引文 斯高帕斯(Scopus)

摘要

In the ovary it has been demonstrated that PGF activates the phospholipase C (PLC)/diacylglycerol/protein kinase C pathway. However, little is known about the downstream signaling events that mediate subsequent cellular responses such as steroidogenesis. The present study was designed to examine the effect of PGF on activation of the mitogen-activated protein kinase (MAPK) signaling pathway and its physiological role in human granulosa-luteal cells (hGLCs). Human GLCs, obtained from women undergoing in vitro fertilization-embryo transfer, were treated with increasing concentrations of PGF (10 nmol/L to 10 μmol/L) for 5 min. For time-course experiments, hGLCs were treated with 1 μmol/L PGF for 1, 5, 10, or 20 min. Western blot analysis, using a monoclonal antibody that detected the phosphorylated forms of extracellular signal-regulated kinases 1 and 2 (p42mapk and p44mapk, respectively), demonstrated that PGF activated MAPK in hGLCs in a dose- and time-dependent manner. Treatment of the cells with neomycin (10 mmol/L; a PLC inhibitor), bisindolylmaleimide I (5 μmol/L; a PKC inhibitor), or PD98059 (50 μmol/L; a MEK inhibitor and a MAPK kinase inhibitor) significantly attenuated the PGF-induced activation of MAPK. In contrast, MAPK activation was not significantly affected by pertussis toxin (200 ng/mL, a Gi inhibitor) pretreatment. To determine the role of MAPK in steroidogenesis, hGLCs were treated with PGF, (1 μmol/L), hCG (1 IU/mL), or PGF, plus hCG in the presence or absence of PD98059. Progesterone levels in the culture medium were examined by RIA. Treatment of hGLCs with PGF significantly inhibited hCG-induced progesterone production. The presence of the MEK inhibitor, PD98059, reversed the inhibitory effect of PGF on hCG-induced progesterone production. To our knowledge, it is the first demonstration of PGF,-induced activation of the MAPK signaling pathway in the human ovary. These results indicated that PGF activated MAPK subsequent to PLC and PKC activation through pertussis toxin-insensitive G protein in hGLCs. Further, we demonstrated that PGF-induced MAPK activation is associated with modulation of progesterone production. These results support the idea that the MAPK signaling pathway is involved in mediating PGF, actions in the human ovary.

原文英語
頁(從 - 到)375-380
頁數6
期刊Journal of Clinical Endocrinology and Metabolism
86
發行號1
DOIs
出版狀態已發佈 - 2001

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

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