PMID- 27539669 OWN - NLM STAT- MEDLINE DCOM- 20180509 LR - 20181202 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 6 DP - 2016 Aug 19 TI - hCG-induced Sprouty2 mediates amphiregulin-stimulated COX-2/PGE2 up-regulation in human granulosa cells: a potential mechanism for the OHSS. PG - 31675 LID - 10.1038/srep31675 [doi] LID - 31675 AB - Sprouty2 (SPRY2) is an important intracellular regulator for epidermal growth factor receptor (EGFR)-mediated ERK1/2 signaling. In human granulosa cells, although SPRY2 is expressed, its regulation and function remains complete unknown and must be defined. Our previous study has shown that human chorionic gonadotropin (hCG)/luteinizing hormone (LH) up-regulates the expression levels of EGF-like growth factor, amphiregulin (AREG), which subsequently contributes to the hCG/LH-induced COX-2 expression and PGE2 production. The aim of the present study was to investigate the effect of hCG on SPRY2 expression and the role of hCG-induced SPRY2 in AREG-stimulated COX-2 expression and PGE2 production in human granulosa cells. Our results demonstrated that the expression of SPRY2 was up-regulated by hCG treatment. Using pharmacological inhibitors and siRNA knockdown, we showed that activation of ERK1/2 signaling was required for hCG-induced up-regulation of SPRY2 expression. Further, SPRY2 knockdown attenuated the AREG-induced COX-2 expression and PGE2 production by inhibiting AREG-activated ERK1/2 signaling. Interestingly, we showed that SPRY2 expression levels were significantly increased in granulosa cells of ovarian hyperstimulation syndrome (OHSS) patients. These results for the first time elucidate the physiological roles of SPRY2 in human granulosa cells and suggest that aberrant expression of SPRY2 may contribute to the pathogenesis of OHSS. FAU - Cheng, Jung-Chien AU - Cheng JC AD - Department of Obstetrics and Gynaecology, Child &Family Research Institute, University of British Columbia, Vancouver, British Columbia, V5Z 4H4, Canada. FAU - Fang, Lanlan AU - Fang L AD - Department of Obstetrics and Gynaecology, Child &Family Research Institute, University of British Columbia, Vancouver, British Columbia, V5Z 4H4, Canada. AD - Reproductive Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. FAU - Chang, Hsun-Ming AU - Chang HM AD - Department of Obstetrics and Gynaecology, Child &Family Research Institute, University of British Columbia, Vancouver, British Columbia, V5Z 4H4, Canada. FAU - Sun, Ying-Pu AU - Sun YP AD - Reproductive Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. FAU - Leung, Peter C K AU - Leung PC AD - Department of Obstetrics and Gynaecology, Child &Family Research Institute, University of British Columbia, Vancouver, British Columbia, V5Z 4H4, Canada. LA - eng GR - 143317/CIHR/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160819 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Membrane Proteins) RN - 0 (SPRY2 protein, human) RN - 9002-67-9 (Luteinizing Hormone) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 1.14.99.1 (PTGS2 protein, human) RN - K7Q1JQR04M (Dinoprostone) SB - IM MH - Cell Line MH - Cyclooxygenase 2/*biosynthesis MH - Dinoprostone/*metabolism MH - Female MH - Gene Expression Regulation/*drug effects MH - Granulosa Cells/*metabolism/pathology MH - Humans MH - Intracellular Signaling Peptides and Proteins/*biosynthesis MH - Luteinizing Hormone/*pharmacology MH - MAP Kinase Signaling System/*drug effects MH - Membrane Proteins/*biosynthesis MH - Ovarian Hyperstimulation Syndrome/*metabolism/pathology PMC - PMC4990972 COIS- The authors declare no competing financial interests. EDAT- 2016/08/20 06:00 MHDA- 2018/05/10 06:00 PMCR- 2016/08/19 CRDT- 2016/08/20 06:00 PHST- 2016/06/07 00:00 [received] PHST- 2016/07/21 00:00 [accepted] PHST- 2016/08/20 06:00 [entrez] PHST- 2016/08/20 06:00 [pubmed] PHST- 2018/05/10 06:00 [medline] PHST- 2016/08/19 00:00 [pmc-release] AID - srep31675 [pii] AID - 10.1038/srep31675 [doi] PST - epublish SO - Sci Rep. 2016 Aug 19;6:31675. doi: 10.1038/srep31675.