Journal
BIOLOGY OF REPRODUCTION
Volume 106, Issue 5, Pages 953-967Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/biolre/ioac020
Keywords
human granulosa cell; interleukin-6; IL-6 trans-signaling; pro gesterone; SOCS3; StAR
Categories
Funding
- Canadian Institutes of Health Research Foundation Scheme [143317]
- National Natural Science Foundation of China [81701412]
- Nature Science Foundation of Hubei Province [2018CFB491]
- Hubei Chenguang Talented Youth Development Foundation Grant
- China Scholarship Council [201806275007]
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IL-6 trans-signaling modulates progesterone production by activating the phosphorylation of JAK2 and STAT3 in human granulosa-lutein cells.
As a critical paracrine regulator of multiple reproductive functions, the cytokine interleukin-6 (IL-6) is expressed in human granulosa cells and can be detected in follicular fluid. At present, the functional role of IL-6 in the regulation of ovarian steroidogenesis is controversial. Moreover, the detailed molecular mechanisms by which IL-6 regulates the production of progesterone in human granulosa cells remain to be elucidated. In the present study, we used primary and immortalized human granulosa-lutein (hGL) cells to investigate the effects of IL-6 on progesterone synthesis and the underlying molecular mechanisms. We found that IL-6 trans-signaling by the combined addition of IL-6 and soluble IL-6 receptor (sIL-6R alpha)-induced steroidogenic acute regulatory expression and progesterone production in hGL cells. Additionally, IL-6/sIL-6R alpha activated the phosphorylation of Janus activated kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3), and the cellular effects were abolished by AG490 (JAK2 inhibitor), C188-9 (STAT3 inhibitor), or siRNA-mediated knockdown of STAT3. IL-6 trans-signaling-induced activation of JAK2/STAT3 also upregulated the expression of suppressor of cytokine signaling 3, which, in turn, negatively regulated the JAK2/STAT3 pathway by suppressing STAT3 activation and its downstream effects. Our findings provide insight into the molecular mechanisms by which IL-6 trans-signaling modulates steroidogenesis in hGL cells. Summary Sentence The IL-6 trans-signaling modulates progesterone production by activating the phosphorylation of JAK2 and STAT3 in human granulosa-lutein cells.
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