The Interleukin-6 trans-signaling promotes progesterone production in human granulosa-lutein cells

Biol Reprod. 2022 Jan 29:ioac020. doi: 10.1093/biolre/ioac020. Online ahead of print.ABSTRACTAs 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-6Rα) induced StAR expression and progesterone production in hGL cells. Additionally, IL-6/sIL-6Rα 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 (SOCS3), 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 ...
Source: Reproductive Biology - Category: Reproduction Medicine Authors: Source Type: research