title: Cytoplasmic localization of Lrh-1 down-regulates ovarian follicular cyp19a1a expression in a teleost, the orange-spotted grouper Epinephelus coioides.
abstract: Liver receptor homolog-1 (LRH-1) is a conserved member of the NR5A subfamily in vertebrates and a potential regulator of estrogen synthesis in the ovarian granulosa cells. An Lrh-1 homologue was obtained from the orange-spotted grouper Epinephelus coioides that contains the conserved structural features of NR5A and is phylogenetically closely related to NR5A2. The expression of the orange-spotted grouper Lrh-1 is tissue-specific with relatively higher levels in the liver and ovary. The immunoreactive signals for Lrh-1 and Cyp19a1a were present in the ovarian follicular cells and germ cells. In the ovarian follicular cells, Lrh-1 was present both in the nucleus and cytoplasm, and colocalized with Cyp19a1a. The expression levels of both increased during vitellogenesis whereas only Cyp19a1a dramatically decreased toward maturation when Lrh-1 was localized almost exclusively to the cytoplasm of the follicular cells. The orange-spotted grouper Lrh-1 could up-regulate cyp19a1a transcription in vitro via the two conserved Ftz-f1 sites in cyp19a1a promoter. Chromatin immunoprecipitation analysis showed that the orange-spotted grouper Lrh-1 could bind cyp19a1a promoter in vivo with a higher abundance in the vitellogenic ovary, whereas the binding was dramatically decreased in the mature ovary. Taken together, the results of present study demonstrate that Lrh-1 plays an important role in up-regulating cyp19a1a gene in the ovarian follicular cells during vitellogenesis, and the sequestration of Lrh-1 to the cytoplasm may down-regulate cyp19a1a expression in the mature ovary. This mechanism for modifying transcriptional roles of the orange-spotted grouper Lrh-1 may shed new light on the regulation of Cyp19a1 expression in other vertebrates as well.
authors.affiliation: Institute of Aquatic Economic Animals, School of Life Sciences, Sun Yat-Sen University, Guangzhou, P.R. China.
authors.forename: Huijie
authors.initials: H
authors.lastname: Lu
authors.affiliation: Institute of Aquatic Economic Animals, School of Life Sciences, Sun Yat-Sen University, Guangzhou, P.R. China.
authors.forename: Shen
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Institute of Aquatic Economic Animals, School of Life Sciences, Sun Yat-Sen University, Guangzhou, P.R. China.
authors.forename: Qiongyou
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Biology Department, School of Life Sciences, Sun Yat-Sen University, Guangzhou, P.R. China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Institute of Aquatic Economic Animals, School of Life Sciences, Sun Yat-Sen University, Guangzhou, P.R. China Biology Department, School of Life Sciences, Sun Yat-Sen University, Guangzhou, P.R. China lsszwm@mail.sysu.edu.cn.
authors.forename: Weimin
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000818:Animals; D003001:Cloning, Molecular; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D010473:Perciformes / Q000502:physiology*; D010802:Phylogeny; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D003577:Cytochrome P-450 Enzyme System
keywords: Cyp19a1a; Lrh-1; orange-spotted grouper Epinephelus coioides; ovarian development