3',5'-cyclic adenosine monophosphate response element binding protein up-regulated cytochrome P450 lanosterol 14alpha-demethylase expression involved in follicle-stimulating hormone-induced mouse oocyte maturation.
Cytochrome P450 lanosterol 14alpha-demethylase (CYP51) is a key enzyme in sterols and steroids biosynthesis that can induce meiotic resumption in mouse oocytes. The present study investigated the expression mechanism and function of CYP51 during FSH-induced mouse cumulus oocyte complexes (COCs) meiotic resumption. FSH increased cAMP-dependent protein kinase (PKA) RIIbeta level and induced cAMP response element-binding protein (CREB) phosphorylation and CYP51 expression in cumulus cells before oocyte meiotic resumption. Moreover, CYP51 and epidermal growth factor (EGF)-like factor [amphiregulin (AR)] expression were blocked by (2)-naphthol-AS-Ephosphate (KG-501) (a drug interrupting the formation of CREB functional complex). KG-501 and RS21607 (a specific inhibitor of CYP51 activity) inhibited oocyte meiotic resumption, which can be partially rescued by progesterone. These two inhibitors also inhibited FSH-induced MAPK phosphorylation. EGF could rescue the suppression by KG-501 but not RS21607. Furthermore, type II PKA analog pairs, N(6)-monobutyryl-cAMP plus 8-bromo-cAMP, increased PKA RIIbeta level and mimicked the action of FSH, including CREB phosphorylation, AR and CYP51 expression, MAPK activation, and oocyte maturation. All these data suggest that CYP51 plays a critical role in FSH-induced meiotic resumption of mouse oocytes. CYP51 and AR gene expression in cumulus cells are triggered by FSH via a type II PKA/CREB-dependent signal pathway. Our study also implicates that CYP51 activity in cumulus cells participates in EGF receptor signaling-regulated oocyte meiotic resumption.
Ning
Gang
G
State Key Laboratories for AgroBiotechnology and Department of Animal Physiology and Biochemistry, College of Biological Sciences, China Agricultural University, Beijing, PR China.
Ouyang
Hong
H
Wang
Songbo
S
Chen
Xiufen
X
Xu
Baoshan
B
Yang
Jiange
J
Zhang
Hua
H
Zhang
Meijia
M
Xia
Guoliang
G
D000818:Animals; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D007654:Ketoconazole / Q000494:pharmacology; D008540:Meiosis; D051379:Mice; D008954:Models, Biological; D009865:Oocytes / Q000166:cytology* / Q000378:metabolism*; D011944:Receptors, Androgen / Q000378:metabolism; D020218:Response Elements; D058886:Sterol 14-Demethylase; D015854:Up-Regulation
D011944:Receptors, Androgen; C018892:2'-deoxy cyclic AMP; D005640:Follicle Stimulating Hormone; D003577:Cytochrome P-450 Enzyme System; D000242:Cyclic AMP; C548415:Cyp51 protein, mouse; D058886:Sterol 14-Demethylase; D007654:Ketoconazole