PMID- 27113901 OWN - NLM STAT- MEDLINE DCOM- 20180903 LR - 20181113 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 6 DP - 2016 Apr 26 TI - Amphiregulin mediates hCG-induced StAR expression and progesterone production in human granulosa cells. PG - 24917 LID - 10.1038/srep24917 [doi] LID - 24917 AB - Progesterone plays critical roles in maintaining a successful pregnancy at the early embryonic stage. Human chorionic gonadotropin (hCG) rapidly induces amphiregulin (AREG) expression. However, it remains unknown whether AREG mediates hCG-induced progesterone production. Thus, the objective of this study was to investigate the role of AREG in hCG-induced progesterone production and the underlying molecular mechanism in human granulosa cells; primary cells were used as the experimental model. We demonstrated that the inhibition of EGFR and the knockdown of AREG abolished hCG-induced steroidogenic acute regulatory protein (StAR) expression and progesterone production. Importantly, follicular fluid AREG levels were positively correlated with progesterone levels in the follicular fluid and serum. Treatment with AREG increased StAR expression and progesterone production, and these stimulatory effects were abolished by EGFR inhibition. Moreover, activation of ERK1/2, but not PI3K/Akt, signaling was required for the AREG-induced up-regulation of StAR expression and progesterone production. Our results demonstrate that AREG mediates hCG-induced StAR expression and progesterone production in human granulosa cells, providing novel evidence for the role of AREG in the regulation of steroidogenesis. FAU - Fang, Lanlan AU - Fang L AD - Reproductive Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China. FAU - Yu, Yiping AU - Yu Y AD - Reproductive Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China. FAU - Zhang, Ruizhe AU - Zhang R AD - Reproductive Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China. FAU - He, Jingyan AU - He J AD - Reproductive Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China. FAU - Sun, Ying-Pu AU - Sun YP AD - Reproductive Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160426 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Amphiregulin) RN - 0 (Chorionic Gonadotropin) RN - 0 (Phosphoproteins) RN - 0 (RNA, Small Interfering) RN - 0 (steroidogenic acute regulatory protein) RN - 4G7DS2Q64Y (Progesterone) SB - IM MH - Adult MH - Amphiregulin/genetics/*metabolism/pharmacology MH - Cells, Cultured MH - Chorionic Gonadotropin/*pharmacology MH - Female MH - Fertilization in Vitro MH - Follicular Fluid/chemistry MH - Gene Expression Regulation MH - Granulosa Cells/drug effects/*metabolism MH - Humans MH - Phosphoproteins/*metabolism MH - Progesterone/*biosynthesis MH - RNA, Small Interfering/genetics MH - Signal Transduction PMC - PMC4845069 EDAT- 2016/04/27 06:00 MHDA- 2018/09/04 06:00 PMCR- 2016/04/26 CRDT- 2016/04/27 06:00 PHST- 2016/01/20 00:00 [received] PHST- 2016/04/07 00:00 [accepted] PHST- 2016/04/27 06:00 [entrez] PHST- 2016/04/27 06:00 [pubmed] PHST- 2018/09/04 06:00 [medline] PHST- 2016/04/26 00:00 [pmc-release] AID - srep24917 [pii] AID - 10.1038/srep24917 [doi] PST - epublish SO - Sci Rep. 2016 Apr 26;6:24917. doi: 10.1038/srep24917.