Amphiregulin mediates hCG-induced StAR expression and progesterone production in human granulosa cells.
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.
Reproductive Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China.
Lanlan
L
Fang
Reproductive Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China.
Yiping
Y
Yu
Reproductive Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China.
Ruizhe
R
Zhang
Reproductive Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China.
Jingyan
J
He
Reproductive Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China.
Ying-Pu
YP
Sun
D000328:Adult; D066258:Amphiregulin / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D005260:Female; D005307:Fertilization in Vitro; D015571:Follicular Fluid / Q000737:chemistry; D005786:Gene Expression Regulation; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D010750:Phosphoproteins / Q000378:metabolism*; D011374:Progesterone / Q000096:biosynthesis*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D000098682:Steroidogenic Acute Regulatory Protein
D066258:Amphiregulin; D006063:Chorionic Gonadotropin; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D000098682:Steroidogenic Acute Regulatory Protein; D011374:Progesterone