title: Human LBP-32/MGR is a repressor of the P450scc in human choriocarcinoma cell line JEG-3.
abstract: Steroid hormones regulate a wide range of physiologic functions in humans. The cholesterol side-chain cleavage enzyme P450scc regulates the initial step of biosynthesis of all steroid hormones. We investigated the expression of P450scc by studying a potential regulator of P450scc, LBP-32/MGR. Using a Northern blot, we found that LBP-32/MGR mRNA was expressed mainly in the human placenta. Using radiation hybrid mapping, we identified LBP-32/MGR on human chromosome 2p25. Recombinant LBP-32/MGR protein bound preferentially to a DNA fragment from the promoter of P450scc in vitro and exhibited clear nuclear localization in transfected cells. Luciferase reporter gene assays showed that LBP-32/MGR specifically repressed transcriptional activation of the human P450scc promoter. Because placental P450scc expression is essential for pregnancy and steroid biosynthesis, the placental expression and transcriptional repressor activity of LBP-32/MGR in JEG-3 cells suggest it has a role as a transcriptional modulator of steroid biosynthesis.
authors.affiliation: Department of Head & Neck Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Y C
authors.initials: YC
authors.lastname: Henderson
authors.forename: M J
authors.initials: MJ
authors.lastname: Frederick
authors.forename: A
authors.initials: A
authors.lastname: Jayakumar
authors.forename: Y
authors.initials: Y
authors.lastname: Choi
authors.forename: M T
authors.initials: MT
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Kang
authors.forename: R
authors.initials: R
authors.lastname: Evans
authors.forename: P M
authors.initials: PM
authors.lastname: Spring
authors.forename: M
authors.initials: M
authors.lastname: Uesugi
authors.forename: G L
authors.initials: GL
authors.lastname: Clayman
mesh_terms: D002461:Cell Line, Transformed; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000502:physiology*; D002889:Chromosomes, Human, Pair 2; D004247:DNA / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: C518352:GRHL1 protein, human; D012333:RNA, Messenger; D011994:Recombinant Proteins; D012097:Repressor Proteins; D004247:DNA; D002786:Cholesterol Side-Chain Cleavage Enzyme