5 years ago

IL-1β up-regulates StAR and progesterone production through the ERK1/2 and p38-mediated CREB signaling pathways in human granulosa-lutein cells.

He Y, Lu Y, Wang Y, Dang X, Sun Y, Wu H, Qi J, Zhu Q, Li X
The pro-inflammatory cytokine interleukin-1β (IL-1β) may be involved in several ovulation-associated events, such as proteases synthesis, prostaglandin production and steroidogenesis in granulosa cells. However, the exact effect of IL-1β on progesterone synthesis in granulosa cells and the underlying mechanism remain unclear. By using cultured granulosa-lutein cells collected from women undergoing in vitro fertilization or intracytoplasmic sperm injection, we found that IL-1β up-regulated steroidogenic acute regulatory protein (StAR) expression and progesterone synthesis in granulosa-lutein cells, which was comparable with luteinizing hormone (LH) effect and could be abolished by an IL-1 receptor antagonist. Moreover, IL-1β activated the phosphorylation of cAMP response element-binding protein (CREB) and knock-down of CREB attenuated the induction of StAR expression and progesterone synthesis by IL-1β in granulosa-lutein cells. Furthermore, IL-1β activated the ERK1/2 and p38 pathways and inhibition of the ERK1/2 and p38 pathways attenuated the IL-1β-induced phosphorylation of CREB, StAR expression and progesterone synthesis in granulosa-lutein cells. In conclusion, IL-1β could up-regulate StAR expression and stimulate progesterone biosynthesis through increase in CREB phosphorylation via activating the ERK1/2 and p38 pathways in human granulosa-lutein cells.

Publisher URL: https://www.ncbi.nlm.nih.gov/pubmed/28651331

DOI: PubMed:28651331

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