title: Gonadotropin-regulated expressions of lanosterol 14alpha-demethylase, sterol Delta14-reductase and C-4 sterol methyl oxidase contribute to the accumulation of meiosis-activating sterol in rabbit gonads.
abstract: Meiosis-activating sterol (MAS), the intermediate of cholesterol biosynthesis, is an important lipophilic molecule mediating gonadotropins' action in inducing oocyte meiotic resumptions in various mammalian species. With respect to MAS's physiological relevance during oocyte maturation in the rabbit, early study has demonstrated that luteinizing hormone (LH), but not follicle stimulating hormone (FSH) can induce FF-MAS accumulation facilitating oocyte maturation in rabbits. However, the potential underlying mechanism for the MAS accumulation in the rabbit gonad remained unclear. We hypothesized that differential expression of MAS synthetic and metabolic enzymes would contribute to the timely MAS accumulation in the rabbit gonad. To address this issue, in the present investigation, we first cloned the cDNAs encoding there pre- and post-MAS enzymes, lanosterol 14alpha-demethylase (CYP51), sterol Delta14-reductase (14-SR) and C-4 sterol methyl oxidase (C4MO), respectively, using rapid amplification of cDNA ends (RACE) cloning, and then performed northern hybridization experiments to explore their expression profiles in the rabbit ovary, testis, and various other tissues. We observed that CYP51 expression was significantly upregulated only by LH/hCG in the antral follicle exhibiting its peak levels in preovulatory follicles; whereas both FSH and LH significantly downregulated 14-SR expression with the progression of antral follicular development. These findings provided here novel evidence that an inverse upregulation of CYP51 and downregulation of 14-SR expression under FSH/LH stimulation functions as the machinery for FF-MAS accumulation in preovulatory follicles prior to ovulation in the rabbit.
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. fcwang@ioz.ac.cn
authors.forename: Fengchao
authors.initials: F
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.forename: Haibin
authors.initials: H
authors.lastname: Wang
authors.forename: Guoliang
authors.initials: G
authors.lastname: Xia
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002782:Cholestenes / Q000378:metabolism*; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006062:Gonadotropins / Q000494:pharmacology*; D006066:Gonads / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D006899:Mixed Function Oxygenases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D006080:Ovarian Follicle / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D010053:Ovary / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D010088:Oxidoreductases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D017422:Sequence Analysis, DNA; D058886:Sterol 14-Demethylase; D013737:Testis / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism
chemical_list: D002782:Cholestenes; D006063:Chorionic Gonadotropin; D006062:Gonadotropins; D012333:RNA, Messenger; C100324:4,4-dimethylcholesta-8,14,24-trienol; D005640:Follicle Stimulating Hormone; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D058886:Sterol 14-Demethylase; C027532:methylsterol monooxygenase; C022672:delta(14)-sterol reductase